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Previous Article | Next Article 
Journal of Bacteriology, January 1999, p. 359-367, Vol. 181, No. 2
Processive Antitermination
Section on Microbial Genetics, Laboratory of
Molecular Genetics, National Institute of Child Health and Human
Development, National Institutes of Health, Bethesda, Maryland
20892-2785,1 and
Institute of Cancer
Research, Columbia University, New York, New York
100322
After initiating synthesis of RNA at
a promoter, RNA polymerase (RNAP) normally continues to elongate the
transcript until it reaches a termination site. Important elements of
termination sites are transcribed before polymerase translocation
stops, and the resulting RNA is an active element of the termination
pathway. Nascent transcripts of intrinsic sites can halt transcription without the assistance of additional factors, and those of
Rho-dependent sites recruit the Rho termination protein to the
elongation complex. In both cases, RNAP, the transcript, and the
template dissociate (reviewed in references 76 and
80).
Termination is rarely, if ever, completely efficient, and the
expression of downstream genes can be controlled by altering the
efficiency of terminator readthrough. Two distinct mechanisms of
elongation control have been reported for bacterial RNA polymerases. In
one, exemplified by attenuation of the his and
trp operons of Salmonella typhimurium and
Escherichia coli, respectively, a single terminator is
inactivated by interaction with an upstream sequence in the transcript,
with a terminator-specific protein, or with a translating ribosome that
follows closely behind RNAP (reviewed in references
35 and 104). In a second, whose
prototype is antitermination of phage Antitermination in
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
MINIREVIEW
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References
early transcription,
polymerase is stably modified to a terminator-resistant form after it
leaves the promoter. In this case, the modified enzyme not only
transcribes through sequential downstream terminators, but also it is
less sensitive to the pause sites that normally delay transcript
elongation. Both pathways are widespread in nature, but in this
minireview we consider only the second, which is known as processive
antitermination (for previous reviews, see references 22, 23,
27, and 32). The recent explosive growth
in our understanding of transcription elongation (reviewed in
references 57, 96, and 99) make this an especially appropriate time to survey regulatory elements that
target the transcription elongation complex.
is induced by two quite distinct mechanisms. The
first is the result of interaction between N protein and its
targets in the early phage transcripts, and the second is the result of
an interaction between the Q protein and its target in the late
phage promoter. We describe the N mechanism first. Lambda N, a small
basic protein of the arginine-rich motif (ARM) (Fig.
1) family of RNA
binding proteins, binds to a 15-nucleotide (nt) stem-loop called BOXB
(17) (Fig. 2). (We will capitalize the names of sites in RNA
and italicize the names of the corresponding DNA sequences; e.g., BOXB
and boxB.) boxB is found twice in the chromosome, once in each of the two early operons (82, 83). It is close to the start point of the PL operon transcript
and just downstream of the first translated gene of the PR
operon. Neither the distance between the transcription start site and boxB, nor the nature of the promoter (at least in the case
of sigma-70-dependent promoters), nor the nature of the terminator is
relevant to N action. Although the boxB sequence is not well conserved in other bacteriophages of the family, most of these phages encode proteins that are analogous to N and have sequences capable of forming BOXB-like structures in their PL and
PR operons. In some cases, it has been shown that these
structures are recognized by the cognate N analogs. It is believed that
this accounts for the phage specificity of N-mediated antitermination.
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FIG. 1.
(A) Alignment of phage N proteins and the HK022 Nun
protein. The color groupings reflect the frequency of amino acid
substitutions in evolutionarily related protein domains: an amino acid
is more likely to be replaced by one in the same color group than by
one in a different color group in related proteins (34). The
amino-proximal ARM regions were aligned by eye and according to the
structures of the P22 and ARMs complexed to their cognate
nut sites (see text and Fig. 2), and the remainder of the
proteins was aligned by ClustalW (38). The dots indicate
gaps introduced to improve the alignment. Aside from the ARM regions,
the proteins fall into three very distantly related (or unrelated)
families: (i) and phage 21; (ii) P22, phage L, and HK97; and (iii)
HK022 Nun. The divergence of Nun from the N proteins is unsurprising
because of their different functions. The sequence database was
searched for additional N homologs with the PSI-BLAST program (3), using each of the listed sequences as a
query, but none were found. Two N proteins were omitted from the
alignment: that of phage H19b, because it differs by only three
conservative substitutions from N of HK97 (E60D, K80E, and R100K)
(3), and that of lambdoid phage 
80 (Phi 80), because it
shows no resemblance to any of the other N proteins, lacking even an
ARM (42, 69). (B) Alignment of phage Q proteins. The
alignments were generated by ClustalW, and the database was searched
for Q homologs as described above. These proteins fall into three very
distantly related (or unrelated) families: (i) and Qin; (ii) H19b,
Dlp12, and phage 21; and (iii) N15 and phage 82. Qin and Dlp12 are
defective lambdoid prophages of E. coli, but it is likely
that their Q proteins are active (see reference 16).
The Q proteins of phages HK022 and P22 were omitted from the alignment
because of their close similarity to that of . A putative and
possibly defective Q, encoded by a sequence located upstream of
Shiga-like toxin I genes in an E. coli isolate
(72) and found by a BLAST search of the translated
nucleotide sequence database, was omitted from the alignment because of
its close similarity to the Q of phage H19B (61).
The structures of complexes between the ARMs of N (residues 1 to
22) and P22 N (residues 14 to 32) and their cognate BOXBs have recently
been determined by nuclear magnetic resonance (15, 48) (Fig.
2). The two complexes, although similar,
show differences that account for the specificity of N-BOXB recognition
(92, 101). Upon binding, the and P22 ARMs adopt a bent
-helix conformation that packs against the BOXB hairpin through
hydrophobic and ionic interactions. Residues in the amino-proximal
segments make multiple base, ribose, and phosphate contacts in the
5'-ascending stem of BOXB without disrupting its regular A-form. The
two stem-proximal residues of both RNA loops form a sheared G · A base pair which is contacted by R7 of N and R19 of P22 N (note
that R19 corresponds to Arg 6 of Fig. 2; see Fig. 2 legend). In the complex, the fourth residue (G) of the GAAGA loop is extruded and the
remaining residues form a GNRA fold similar to the base-stacked GAAA
tetraloop reported in a number of important RNA structures (Fig. 2).
P22 N also creates a GNRA fold, but this is accomplished by extrusion of the third residue (C) of the GACAA loop. In contrast to the extruded
G residue in BOXB-, which is not close to N, the extruded C
residue in BOXB-P22 makes contacts with residues in the
carboxyl-proximal segment of P22 N. The structure of the N complex
is stabilized by an important stacking interaction between W18 and the
second residue (A) in the BOXB- loop. This interaction is not found in the P22 complex. Formation of the GNRA fold is essential for N
binding, and mutations in loop residues 1, 3, and 5 that prevent tetraloop formation block N binding (17). The structure of
the complex between the BOXB of phage 21 and its cognate N protein must
be substantially different than the complexes described above because
the BOXB-21 loop (TCTAACCG) cannot be folded into a GNRA tetraloop. However, the HK022 Nun protein, which recognizes BOXB
(see below), probably does so in a way that resembles that of (18). If so, A3, R7, and W18 of N, all of which make base contacts in BOXB, probably correspond to S27, R31, and Y42 of Nun
(Fig. 1).
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Promoter proximal to each of the boxB sequences is
boxA, which is also important for antitermination by N
(70) (Fig. 2). boxA-like sequences are also found
in corresponding positions in several other lambdoid phages. Together,
the two boxes constitute a nut (for N utilization) site,
which contains all of the cis-acting elements required for
N-dependent antitermination. In the presence of N, polymerase becomes
termination resistant after transcription of nut
(7a). Antitermination can still be detected after polymerase has read through thousands of base pairs and many sequential
terminators. This implies that the N-dependent modification to
polymerase that occurs after transcription of nut is stable.
BOXA is the loading site for the E. coli S10 (or NusE) and
NusB proteins (62). In association with two additional
E. coli factors, NusA and NusG, an antitermination complex
containing N and NUT is formed with RNAP. It is clear that N is the
active factor in the complex, since at sufficiently high
concentrations, N suppresses transcription termination in vitro in the
absence of nut or the Nus factors (24, 75).
However, the additional components increase the stability of the
antitermination complex and reduce the level of N that is needed
(24, 54). The RNAP subunit might also have a specific
role in N-mediated antitermination. Mutations that alter the
carboxyl-terminal domain of the RNAP subunit have been reported to
enhance or inhibit N antitermination in vivo, according to the nature
and location of the mutation (68, 85). However, deletion of
the carboxyl-terminal domain of does not affect N-dependent
antitermination in vitro, perhaps indicating that some regulatory
component is missing from the reaction (53).
The formation of the complete antitermination complex can occur in
discrete steps (56). Initially, NusA binds to an N-BOXB complex. This binding requires extrusion of the loop residue of BOXB.
Thus, a BOXB tetraloop mutant (GAAGA 
GAAA) binds N but does not form an N-BOXB-NusA complex, as demonstrated by supershift experiments (17, 55). A core complex of BOXB, N, NusA, and RNAP can read through terminators located close to the NUT site in
vitro. In the absence of N and NUT, NusA binds to the elongation complex near the 3'-OH terminus of the nascent RNA chain and enhances pausing and termination (53).
Processive antitermination requires the complete antitermination
complex. The assembly of NusB, S10, and NusG onto the core complex
involves nt 2 to 7 of BOXA (CGCUCUUACACA),
as well as the carboxyl-terminal region of N, which interacts
with RNAP (56). The role of NusG in the N antitermination
reaction is not clear. NusG binds to termination factor Rho and to RNAP
(49, 54). It stimulates the rate of transcription elongation
and is required for the activity of certain Rho-dependent terminators
(12, 93). NusG is a component of the complete
antitermination complex and enhances N antitermination in vitro.
However, alteration of BOXA to a variant called BOXA consensus
(CGCUCUUUAACA) allows NusB and S10 to assemble in the
absence of NusG (56). Furthermore, depletion of NusG has no
effect on N antitermination in vivo, and unlike nusA,
nusB, and nusE, no point mutations in
nusG that block N activity have been isolated. A NusG
homolog, RfaH, enhances elongation of several transcripts in E. coli and S. typhimurium (see below). The possibility
that RfaH and NusG are redundant for N antitermination has not yet been
tested, although for several other functions, the two proteins are not interchangeable.
The function of BOXA in N-mediated antitermination is likewise not
entirely clear. Point mutations in boxA that decrease or
increase antitermination efficiency have been isolated (70, 73,
84). On the other hand, deletion of the boxA region
does not inhibit antitermination in vivo. Instead, antitermination no
longer requires NusB (73). To account for this, it has been proposed that BOXA is not directly required for antitermination but
instead is the site of interplay between inhibitory and anti-inhibitory factors. According to this model, boxA point mutations that
reduce antitermination eliminate binding of the anti-inhibitor but not the inhibitor. boxA deletions eliminate binding of the
inhibitor, and therefore, the anti-inhibitor, presumably NusB, is no
longer needed. This notion is supported by an experiment in which
high-level transcription of an antitermination-defective
boxA point mutant activated growth in trans of a
phage carrying the same mutation in a nusB mutant host,
presumably by titrating the inhibitor (73). In a similar
experiment, high-level transcription of a consensus BOXA inhibited
growth of a phage carrying a wild-type boxA, probably by
titrating NusB (28). However, the role of NusB is likely to
go beyond that of an anti-inhibitor, and that of BOXA is likely to go
beyond that of a site for the interplay of inhibitory and anti-inhibitory factors. In vitro studies with purified proteins show
that point mutations in boxA impede the assembly of the
antitermination complex even in the absence of a known inhibitor
(56), and NusB stimulates processive antitermination in such
a system (24, 54). In addition, the role of BOXA in
antitermination of Rho-dependent terminators in bacterial rRNA operons
appears to be more central than it is in , raising the possibility
that BOXA contributes to antitermination in a way that is at least
partially independent of BOXB (32) (see below).
Surprisingly, the nut sites are also components in a
transcription termination pathway. In this pathway, N is replaced by Nun, a protein encoded by a relative of , phage HK022 (see below) (67, 78). Nun converts antitermination into termination.
Other components of the two pathways, notably NusA, NusB, S10, NusG, BOXA, and BOXB, are shared. The sequence similarity of Nun to proteins
of the N family, although weak, includes the amino-proximal ARM region
(Fig. 1). This is unsurprising because Nun, like N, binds
specifically to BOXB and requires the same BOXB nucleotides for
biological function (8, 18). In vivo, Nun terminates transcription just distal to the nut sites (78,
88). In vitro, Nun arrests RNAP translocation at several
positions downstream of nut (39). The arrested
elongation complexes contain the 3' ends of the nascent transcripts in
the polymerase active center, and this site remains enzymatically
active: the 3' nucleotide can be removed by pyrophosphorolysis and
restored by addition of the appropriate nucleoside triphosphate
(40). However, forward and backward translocation of RNAP is
blocked. The Nus factors increase the efficiency of transcription
arrest but are not essential if the concentration of Nun is elevated.
Nun-dependent release of arrested RNAP from the template and transcript
has not been observed in a purified transcription system, presumably
because a factor(s) is missing. The differences between N and Nun that lead to their opposed biological activities are unknown. However, the
amino-proximal regions, which contain the ARMs, can be interchanged between the two proteins without altering their functions
(36). Therefore, the functional differences are in the
carboxyl-terminal 50 to 75% of the proteins. Of particular note is the
presence of three C-terminal His residues, specific to Nun. These
residues form part of a Zn2+ binding motif that is required
for Nun activity (100). The carboxyl-terminal regions of N
and Nun may bind different RNAP subunits; certain rpoC
(
') mutations block Nun but not N activity (81).
A second phage-encoded factor, Q protein, induces antitermination
in the late operon (25, 37). Lambda Q, like N, has
functional analogs in other phages (Fig. 1). These late antiterminators probably act by a similar mechanism, although some are only distantly related or unrelated to Q (30, 33, 102). Initially, Q
binds to a region within the PR' promoter
(105). Interaction with RNAP can be detected when the
transcription complex pauses at +16, downstream of a site similar to
the extended 
10 sequence of some sigma-70 promoters (31,
77). The presence of the sigma-70 subunit of RNAP holoenzyme is
essential for pausing and for Q-mediated antitermination: RNAP core
enzyme that has been artificially paused at +16 by omission of the
appropriate nucleoside triphosphate cannot be modified by Q. In
addition, sigma-70 mutants that are unable to support Q-mediated
antitermination have been isolated (43b). However, once Q
has interacted with RNAP holoenzyme, sigma-70 is no longer needed for
stable association of Q with the elongation complex. Although
antitermination by Q is enhanced by NusA in vitro, it is not clear if
the Q reaction has additional requirements in vivo. How Q modifies RNAP
function is likewise unknown.
Processive antitermination can be mediated by RNA as well as proteins.
Coliphage HK022, alone among the known lambdoid phages, does not encode
an analog to N (66). Instead, it promotes antitermination of early phage transcription through the direct action
of transcribed sequences called put (for polymerase
utilization) sites (Fig. 3) (20,
43). There are two closely related put sites, one
located in the PL operon and the other located in the PR operon, roughly corresponding to the positions of the
nut sequences in and in other relatives.
put sites act in cis to promote readthrough of
downstream terminators in the absence of all HK022 proteins. The
put transcripts are predicted to form two stem-loops separated by a single unpaired nucleotide. This prediction is supported
by mutational studies and the pattern of sensitivity of the two RNAs to
cleavage with single- and double-strand-specific endoribonucleases
(7). RNA structure is critical to antitermination because
mutations that prevent the formation of base pairs in the stems reduce
function, and these mutations can be suppressed by additional mutations
that restore base pairing (43). Like N and Q, the PUT
sequences suppress polymerase pausing and promote processive
antitermination in a purified in vitro transcription system. In
contrast to N, no phage or auxiliary bacterial factors are
required. The only mutations known to block PUT-mediated
antitermination change highly conserved amino acids located in a
cysteine-rich amino-proximal domain of the RNAP ' subunit
(20). Strains carrying these mutations are unable to support
lytic growth of HK022 but are normal in all other respects tested,
including lytic growth of and other relatives. The
phage-restricted phenotypes conferred by these mutations suggests that
they alter a domain of RNAP-' that interacts specifically with
nascent PUT RNA in the transcription elongation complex, but this idea
has not been directly tested. The stability of the putative PUT-RNAP
interaction and the nature of the PUT-induced modification to the
elongation complex are unknown.
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So far, factor-independent antitermination is unique to
phage HK022. Both factor-independent and -dependent modes of
antitermination are efficient, processive, and well-suited to their
tasks. Indeed, the isolation and characterization of a hybrid phage
that contains the early promoters and put sites of phage
HK022 fused to the PL and PR operons of show that the HK022 antitermination pathway suppresses the terminators to the extent necessary for normal lytic growth and lysogen
formation by the hybrid (66). In addition, late gene
expression in phage HK022 is activated by a Q-dependent antitermination
pathway that is very closely related to that of (4). The
relative advantages of the PUT and N-NUT antitermination mechanisms and
the evolutionary reasons for their adoption by different closely
related phages are obscure. Recent work suggests that the activity of
N-dependent antitermination is autoregulated so as to couple the
lysogeny-lysis decision of infected cells to their growth phase
(21a). It is not clear if the put-dependent antitermination activity of HK022 is regulated. However, HK022 has
devoted the resources saved by the dispensability of N to the
production of Nun, a protein that prevents the growth of a potential
competitor by coopting a component of its antitermination system (see above).
Processive antitermination was first discovered in a bacteriophage, but
examples have since been found in bacterial operons. The E. coli
rrn operons are regulated by an antitermination mechanism that is
dependent on sites that are closely related to boxA and
located promoter proximal to the 16S and 23S structural genes in each
operon (1, 50, 58; reviewed in reference
21). The sequences of the rrn BOXA sites
are more similar to the bacteriophage consensus than is that of ,
and they bind NusB-S10 more efficiently (62). Although
stem-loop structures analogous to BOXB are found promoter proximal to
the BOXA sites, they are not essential for antitermination. An
rrn BOXA sequence confers full antitermination activity
against Rho-dependent but not against intrinsic terminators (2,
9). BOXA also increases the rate of transcription elongation by
RNAP (97). Point mutations in BOXA induce premature
transcription termination. rrn antitermination requires NusB
in vivo, as shown by a NusB depletion experiment (89). NusA
stimulates the elongation rate of rrn RNA chains carrying
BOXA (98). A role for NusA is further suggested by the
observation that the nusA10(Cs) mutation inhibits both
antitermination and the rate of transcription elongation in an
rrn operon (98). The role of other Nus factors in
rrn regulation in vivo is not clear. In vitro, an
antitermination complex that includes NusA, NusB, S10, and NusG forms
at the BOXA sequence of rrnG, but these components are not
sufficient for antitermination by themselves (89). An
additional factor or factors that can be supplied by a cellular extract
are required, but their identities are unknown.
A second bacterial elongation control pathway depends on the RfaH protein, a NusG homolog (5, 6, 91). RfaH and a cis-acting promoter-proximal sequence element, ops (for operon polarity suppressor, also called JUMPstart), increase the expression of several bacterial operons. The products of these operons affect the production and transport of components located on the outside of the inner membrane, such as lipopolysaccharide core, exopolysaccharide, F pili, and hemolysin. These operons are relatively long, with several genes and intergenic terminators. RfaH and ops appear to function together, since mutational inactivation of both elements does not have an additive effect on gene expression. The two elements are thought to act by suppressing termination. First, transcription is increased distal to the promoter but not proximal to a terminator. Second, stimulation of gene expression is not promoter specific. Third, an rfaH mutation can be suppressed by a mutation that reduces the activity of transcription termination factor Rho (26). Purified RfaH stimulates transcription promoter distal to an intrinsic terminator when added to a crude bacterial extract programmed with an ops-containing template. However, it has not been shown that the increase results from elongation of transcripts that would otherwise have been terminated. Nevertheless, the requirement for a cis-acting site, the ability of the site to act at a distance from terminators, and the homology of RfaH and NusG suggest common elements with the mechanisms of N-dependent antitermination.
Phage P4 has an entirely different mechanism of controlling elongation.
It encodes a protein, Psu (for polarity suppressor), that reduces
termination by E. coli Rho factor (51, 94).
Unlike N and Q, Psu does not require cis-acting sites to
antiterminate and is specific for Rho-dependent terminators. Extracts
of cells that contain Psu are deficient in termination at Rho-dependent terminators, and termination can be restored by adding Rho to the
extracts (52). Psu does not act by reducing the level of Rho
protein, but it interferes, directly or indirectly, with Rho action.
The importance of Rho inactivation in the life cycle of P4 is unclear.
Psu stimulates lytic growth of P4, but this is likely to be the result
of incorporation of Psu into the P4 capsid rather than (or in addition
to) activation of transcription of essential genes that lie downstream
of Rho-dependent terminators (41). The only known protein
that is similar to Psu is encoded by a P4 relative, retronphage R73
(41).
How do terminators and antiterminators act? Do the antitermination pathways described here have common steps? We cannot yet answer these questions, but a brief discussion of what we think we know about the structure and stability of the elongation complex should limit the possibilities and provide a basis for speculation. The active bacterial elongation complex consists of core RNAP, template, and RNA product. The 3' end of the RNA is engaged in the active site of the enzyme, the following ~8 nt are hybridized to the template strand of the DNA, and the next ~9 nt remain closely associated with RNAP (64). About 17 nt of the nontemplate DNA strand are separated from the template strand in the transcription bubble. Elongation complexes can also contain NusA and/or NusG. These proteins, which increase the stability of the N-mediated antitermination complex (see above), have different effects on elongation. NusA decreases and NusG increases the elongation rate, and both proteins alter termination efficiency in a terminator-specific manner (13, 14, 86; see reference 76).
An elongation complex, unless located at a terminator, is extraordinarily stable, even when translocation is prevented by removal of substrates. Recent observations suggest that this stability depends mainly on interactions between RNAP and the RNA-DNA hybrid as well as between polymerase and the downstream duplex DNA template (63, 87). Nascent RNA emerging from the hybrid region and upstream duplex DNA do not appear to be required. The strength of the RNA-DNA hybrid is believed to assure the lateral stability of the complex. Reducing the strength of the RNA-DNA bonds, for example by incorporation of nucleotide analogs, favors backsliding of RNAP on the template, with consequent disengagement of the 3' RNA end from the active site, and concerted retreat of the RNA-DNA hybrid region from the 3' end (65). Such a disengaged complex retains its resistance to dissociation and is capable of resuming elongation if the original or a newly created 3' end reengages with the active site (10, 44, 45, 65, 71, 95).
Intrinsic terminators consist of a guanine- and cytosine-rich RNA hairpin stem immediately followed by a short uracil-rich segment within which termination can occur. If termination does not occur at this point, polymerase continues to elongate the transcript with normal processivity until it reaches the next terminator. Neither the stem nor the uracil-rich segment is sufficient for termination, although either can transiently slow elongation. The weakness of base pairing between rU and dA destabilizes the RNA-DNA hybrid in the uracil-rich segment, and this probably contributes to termination. Formation of the hairpin stem as nascent terminator RNA emerges from polymerase destabilizes the RNA-DNA hybrid and interrupts contacts between the emerging nascent RNA and RNAP (62a). It might also interfere with the stabilizing interactions between RNAP and the hybrid or those between RNAP and the downstream region of the template. Cross-linking of nucleic acid to RNAP suggests that both the downstream DNA and the nascent RNA that emerges from the hybrid region, and within which the terminator hairpin might form, are located close to the same regions of the enzyme (64). Conversely, modifications that render RNAP termination resistant could prevent the terminator stem from destabilizing one or more of these targets, at least while the 3' end of the RNA is within the uracil-rich segment of the terminator.
The N and Q proteins and HK022 PUT RNA also suppress Rho-dependent
terminators (43a, 79, 103) which, in contrast to intrinsic
terminators, lack a precisely determined termination point. Rho is an
RNA-dependent ATPase that binds to cytosine-rich, unstructured regions
in nascent RNA and acts preferentially to terminate elongation
complexes that are paused at nearby downstream sites (19, 29, 46,
47, 59, 60). Rho possesses RNA-DNA helicase activity, and this
activity is directional, unwinding DNA paired to the 3' end of the RNA
molecule (11, 90). This corresponds to the location of the
hybrid and of RNAP in an active ternary elongation complex. The ability
of antiterminators to suppress Rho-dependent and -independent
terminators suggests that they prevent a step that is common to both
classes. Given the helicase activity of Rho, a likely candidate for
this step is disruption of the RNA-DNA hybrid. However, other
candidates, such as destabilization of RNAP-template or RNAP-hybrid
interactions, are also plausible. Alternatively, the ability of N, Q,
and PUT to suppress RNAP pausing (31, 43, 54, 74) suggests
that they prevent Rho-dependent termination by accelerating polymerase away from Rho bound at upstream RNA sites. This explanation raises the
problem of why NusG, which also accelerates polymerase, enhances rather
than suppresses Rho-dependent termination (see above). Clearly, the
molecular details of processive antitermination remain poorly
understood despite the 30 years that have elapsed since its discovery.
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ACKNOWLEDGMENTS |
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Thanks to Donald Court, Asis Das, David Friedman, Rodney King, Orna Resnekov, and Randy Watnick for their comments on the manuscript.
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FOOTNOTES |
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* Corresponding author. Mailing address: Section on Microbial Genetics, Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2785. Phone: (301) 496-3555. Fax: (301) 496-0243. E-mail: wia{at}cu.nih.gov.
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REFERENCES |
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References
|
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| 1. |
Aksoy, S.,
C. L. Squires, and C. Squires.
1984.
Evidence for antitermination in Escherichia coli rRNA transcription.
J. Bacteriol.
159:260-264 |
| 2. | Albrechtsen, B., C. L. Squires, S. Li, and C. Squires. 1990. Antitermination of characterized transcriptional terminators by the Escherichia coli rrnG leader region. J. Mol. Biol. 213:123-134[Medline]. |
| 3. |
Altschul, S. F.,
T. L. Madden,
A. A. Schaffer,
J. Zhang,
Z. Zhang,
W. Miller, and D. J. Lipman.
1997.
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
Nucleic Acids Res.
25:3389-3402 |
| 4. | Atkinson, B. L., and M. E. Gottesman. 1992. The Escherichia coli rpoB60 mutation blocks antitermination by coliphage HK022 Q-function. J. Mol. Biol. 227:29-37[Medline]. |
| 5. | Bailey, M. J., C. Hughes, and V. Koronakis. 1996. Increased distal gene transcription by the elongation factor RfaH, a specialized homologue of NusG. Mol. Microbiol. 22:729-737[Medline]. |
| 6. | Bailey, M. J., C. Hughes, and V. Koronakis. 1997. RfaH and the ops element, components of a novel system controlling bacterial transcription elongation. Mol. Microbiol. 26:845-851[Medline]. |
| 7. | Banik-Maiti, S., R. A. King, and R. A. Weisberg. 1997. The antiterminator RNA of phage HK022. J. Mol. Biol. 272:677-687[Medline]. |
| 7a. | Barik, S., B. Ghosh, W. A. Whalen, D. Lazinski, and A. Das. 1987. An antitermination protein engages the elongating transcription apparatus at a promoter-proximal recognition site. Cell 50:885-899[Medline]. |
| 8. |
Baron, J., and R. A. Weisberg.
1992.
Mutations of the phage lambda nutL region that prevent the action of Nun, a site-specific transcription termination factor.
J. Bacteriol.
174:1983-1989 |
| 9. | Berg, K. L., C. Squires, and C. L. Squires. 1989. Ribosomal RNA operon anti-termination. Function of leader and spacer region box B-box A sequences and their conservation in diverse micro-organisms. J. Mol. Biol. 209:345-358[Medline]. |
| 9a. |
Beutin, L.,
P. A. Manning,
M. Achtman, and N. Willetts.
1981.
sfrA and sfrB products of Escherichia coli K-12 are transcriptional control factors.
J. Bacteriol.
145:840-844 |
| 10. | Borukhov, S., V. Sagitov, and A. Goldfarb. 1993. Transcript cleavage factors from E. coli. Cell 72:459-466[Medline]. |
| 11. | Brennan, C. A., A. J. Dombroski, and T. Platt. 1987. Transcription termination factor rho is an RNA-DNA helicase. Cell 48:945-952[Medline]. |
| 12. |
Burns, C. M., and J. P. Richardson.
1995.
NusG is required to overcome a kinetic limitation to Rho function at an intragenic terminator.
Proc. Natl. Acad. Sci. USA
92:4738-4742 |
| 13. | Burns, C. M., L. V. Richardson, and J. P. Richardson. 1998. Combinatorial effects of NusA and NusG on transcription elongation and Rho-dependent termination in Escherichia coli. J. Mol. Biol. 278:307-316[Medline]. |
| 14. |
Burova, E.,
S. C. Hung,
V. Sagitov,
B. L. Stitt, and M. E. Gottesman.
1995.
Escherichia coli NusG protein stimulates transcription elongation rates in vivo and in vitro.
J. Bacteriol.
177:1388-1392 |
| 15. | Cai, Z., A. Gorin, R. Frederick, X. Ye, W. Hu, A. Majumdar, A. Kettani, and D. J. Patel. 1998. Solution structure of P22 transcriptional antitermination N peptide-boxB RNA complex. Nat. Struct. Biol. 5:203-212[Medline]. |
| 16. | Campbell, A. M. 1996. Cryptic prophages, p. 2041-2046. In F. C. Neidhardt, R. Curtiss III, J. L. Ingraham, E. C. C. Lin, K. B. Low, B. Magasanik, W. S. Reznikoff, M. Riley, M. Schaechter, and H. E. Umbarger (ed.), Escherichia coli and Salmonella: cellular and molecular biology. ASM Press, Washington, D.C. |
| 17. |
Chattopadhyay, S.,
J. Garcia-Mena,
J. DeVito,
K. Wolska, and A. Das.
1995.
Bipartite function of a small RNA hairpin in transcription antitermination in bacteriophage lambda.
Proc. Natl. Acad. Sci. USA
92:4061-4065 |
| 18. |
Chattopadhyay, S.,
S. C. Hung,
A. C. Stuart,
A. G. Palmer III,
J. Garcia-Mena,
A. Das, and M. E. Gottesman.
1995.
Interaction between the phage HK022 Nun protein and the nut RNA of phage lambda.
Proc. Natl. Acad. Sci. USA
92:12131-12135 |
| 19. | Chen, C. Y., G. R. Galluppi, and J. P. Richardson. 1986. Transcription termination at lambda tR1 is mediated by interaction of rho with specific single-stranded domains near the 3' end of cro mRNA. Cell 46:1023-1028[Medline]. |
| 20. |
Clerget, M.,
D. J. Jin, and R. A. Weisberg.
1995.
A zinc binding region in the ' subunit of RNA polymerase is involved in antitermination of early transcription of phage HK022.
J. Mol. Biol.
248:768-780[Medline].
|
| 21. |
Condon, C.,
C. Squires, and C. L. Squires.
1995.
Control of rRNA transcription in Escherichia coli.
Microbiol. Rev.
59:623-645 |
| 21a. | Court, D. Personal communication. |
| 22. |
Das, A.
1992.
How the phage lambda N gene product suppresses transcription termination: communication of RNA polymerase with regulatory proteins mediated by signals in nascent RNA.
J. Bacteriol.
174:6711-6716 |
| 23. | Das, A. 1993. Control of transcription termination by RNA-binding proteins. Annu. Rev. Biochem. 62:893-930[Medline]. |
| 24. |
DeVito, J., and A. Das.
1994.
Control of transcription processivity in phage lambda: Nus factors strengthen the termination-resistant state of RNA polymerase induced by N antiterminator.
Proc. Natl. Acad. Sci. USA
91:8660-8664 |
| 25. | Dove, W. F. 1966. Action of the lambda chromosome. I. Control of functions late in bacteriophage development. J. Mol. Biol. 19:187-201[Medline]. |
| 26. |
Farewell, A.,
R. Brazas,
E. Davie,
J. Mason, and L. I. Rothfield.
1991.
Suppression of the abnormal phenotype of Salmonella typhimurium rfaH mutants by mutations in the gene for transcription termination factor Rho.
J. Bacteriol.
173:5188-5193 |
| 27. | Friedman, D. I., and D. L. Court. 1995. Transcription antitermination: the lambda paradigm updated. Mol. Microbiol. 18:191-200[Medline]. |
| 28. |
Friedman, D. I.,
E. R. Olson,
L. L. Johnson,
D. Alessi, and M. G. Craven.
1990.
Transcription-dependent competition for a host factor: the function and optimal sequence of the phage lambda boxA transcription antitermination signal.
Genes Dev.
4:2210-2222 |
| 29. |
Galloway, J. L., and T. Platt.
1988.
Signals sufficient for rho-dependent transcription termination at trp t' span a region centered 60 base pairs upstream of the earliest 3' end point.
J. Biol. Chem.
263:1761-1767 |
| 30. |
Goliger, J. A., and J. W. Roberts.
1987.
Bacteriophage 82 gene Q and Q protein. Sequence, overproduction, and activity as a transcription antiterminator in vitro.
J. Biol. Chem.
262:11721-11725 |
| 31. | Grayhack, E. J., X. J. Yang, L. F. Lau, and J. W. Roberts. 1985. Phage lambda gene Q antiterminator recognizes RNA polymerase near the promoter and accelerates it through a pause site. Cell 42:259-269[Medline]. |
| 32. | Greenblatt, J., J. R. Nodwell, and S. W. Mason. 1993. Transcriptional antitermination. Nature 364:401-406[Medline]. |
| 33. |
Guo, H. C.,
M. Kainz, and J. W. Roberts.
1991.
Characterization of the late-gene regulatory region of phage 21.
J. Bacteriol.
173:1554-1560 |
| 34. |
Henikoff, S., and J. G. Henikoff.
1992.
Amino acid substitution matrices from protein blocks.
Proc. Natl. Acad. Sci. USA
89:10915-10919 |
| 35. | Henkin, T. M. 1996. Control of transcription termination in prokaryotes. Annu. Rev. Genet. 30:35-57[Medline]. |
| 36. | Henthorn, K. S., and D. I. Friedman. 1996. Identification of functional regions of the Nun transcription termination protein of phage HK022 and the N antitermination protein of phage gamma using hybrid nun-N genes. J. Mol. Biol. 257:9-20[Medline]. |
| 37. | Herskowitz, I., and E. R. Signer. 1970. A site essential for expression of all late genes in bacteriophage lambda. J. Mol. Biol. 47:545-556[Medline]. |
| 38. | Higgins, D. G., J. D. Thompson, and T. J. Gibson. 1996. Using CLUSTAL for multiple sequence alignments. Methods Enzymol. 266:383-402[Medline]. |
| 39. | Hung, S. C., and M. E. Gottesman. 1995. Phage HK022 Nun protein arrests transcription on phage lambda DNA in vitro and competes with the phage lambda N antitermination protein. J. Mol. Biol. 247:428-442[Medline]. |
| 40. |
Hung, S. C., and M. E. Gottesman.
1997.
The Nun protein of bacteriophage HK022 inhibits translocation of Escherichia coli RNA polymerase without abolishing its catalytic activities.
Genes Dev.
11:2670-2678 |
| 41. | Isaksen, M. L., S. T. Rishovd, R. Calendar, and B. H. Lindqvist. 1992. The polarity suppression factor of bacteriophage P4 is also a decoration protein of the P4 capsid. Virology 188:831-839[Medline]. |
| 42. | Kanemoto, K., S. Tanaka, T. Miyashita, and A. Matsushiro. 1986. Identification and purification of the N gene product of bacteriophage phi 80. Mol. Gen. Genet. 205:523-529[Medline]. |
| 43. | King, R. A., S. Banik-Maiti, D. J. Jin, and R. A. Weisberg. 1996. Transcripts that increase the processivity and elongation rate of RNA polymerase. Cell 87:893-903[Medline]. |
| 43a. | King, R. A., and R. A. Weisberg. Unpublished results. |
| 43b. |
Ko, D. C.,
M. T. Marr,
J. Guo, and J. W. Roberts.
1998.
A surface of Escherichia coli sigma-70 required for promoter function and antitermination by phage lambda Q protein.
Genes Dev.
12:3276-3285 |
| 44. |
Komissarova, N., and M. Kashlev.
1997.
Transcriptional arrest: Escherichia coli RNA polymerase translocates backward, leaving the 3' end of the RNA intact and extruded.
Proc. Natl. Acad. Sci. USA
94:1755-1760 |
| 45. |
Komissarova, N., and M. Kashlev.
1997.
RNA polymerase switches between inactivated and activated states by translocating back and forth along the DNA and the RNA.
J. Biol. Chem.
272:15329-15338 |
| 46. |
Lau, L. F.,
J. W. Roberts, and R. Wu.
1982.
Transcription terminates at lambda tR1 in three clusters.
Proc. Natl. Acad. Sci. USA
79:6171-6175 |
| 47. |
Lau, L. F.,
J. W. Roberts, and R. Wu.
1983.
RNA polymerase pausing and transcript release at the lambda tR1 terminator in vitro.
J. Biol. Chem.
258:9391-9397 |
| 48. | Legault, P., J. Li, J. Mogridge, L. E. Kay, and J. Greenblatt. 1998. NMR structure of the bacteriophage lambda N peptide/boxB RNA complex: recognition of a GNRA fold by an arginine-rich motif. Cell 93:289-299[Medline]. |
| 49. |
Li, J.,
S. W. Mason, and J. Greenblatt.
1993.
Elongation factor NusG interacts with termination factor rho to regulate termination and antitermination of transcription.
Genes Dev.
7:161-172 |
| 50. | Li, S. C., C. L. Squires, and C. Squires. 1984. Antitermination of E. coli rRNA transcription is caused by a control region segment containing lambda nut-like sequences. Cell 38:851-860[Medline]. |
| 51. |
Linderoth, N. A., and R. L. Calendar.
1991.
The Psu protein of bacteriophage P4 is an antitermination factor for rho-dependent transcription termination.
J. Bacteriol.
173:6722-6731 |
| 52. | Linderoth, N. A., G. Tang, and R. Calendar. 1997. In vivo and in vitro evidence for an anti-Rho activity induced by the phage P4 polarity suppressor protein Psu. Virology 227:131-141[Medline]. |
| 53. | Liu, K., Y. Zhang, K. Severinov, A. Das, and M. M. Hanna. 1996. Role of Escherichia coli RNA polymerase alpha subunit in modulation of pausing, termination and anti-termination by the transcription elongation factor NusA. EMBO J. 15:150-161[Medline]. |
| 54. |
Mason, S. W.,
J. Li, and J. Greenblatt.
1992.
Host factor requirements for processive antitermination of transcription and suppression of pausing by the N protein of bacteriophage lambda.
J. Biol. Chem.
267:19418-19426 |
| 55. |
Mogridge, J.,
T. F. Mah, and J. Greenblatt.
1995.
A protein-RNA interaction network facilitates the template-independent cooperative assembly on RNA polymerase of a stable antitermination complex containing the lambda N protein.
Genes Dev.
9:2831-2845 |
| 56. |
Mogridge, J.,
T. F. Mah, and J. Greenblatt.
1998.
Involvement of boxA nucleotides in the formation of a stable ribonucleoprotein complex containing the bacteriophage lambda N protein.
J. Biol. Chem.
273:4143-4148 |
| 57. |
Mooney, R. A.,
I. Artsimovitch, and R. Landick.
1998.
Information processing by RNA polymerase: recognition of regulatory signals during RNA chain elongation.
J. Bacteriol.
180:3265-3275 |
| 58. |
Morgan, E. A.
1986.
Antitermination mechanisms in rRNA operons of Escherichia coli.
J. Bacteriol.
168:1-5 |
| 59. |
Morgan, W. D.,
D. G. Bear, and P. H. von Hippel.
1983.
Rho-dependent termination of transcription. II. Kinetics of mRNA elongation during transcription from the bacteriophage lambda PR promoter.
J. Biol. Chem.
258:9565-9574 |
| 60. |
Morgan, W. D.,
D. G. Bear, and P. H. von Hippel.
1983.
Rho-dependent termination of transcription. I. Identification and characterization of termination sites for transcription from the bacteriophage lambda PR promoter.
J. Biol. Chem.
258:9553-9564 |
| 61. | Neely, M. N., and D. I. Friedman. 1998. Functional and genetic analysis of regulatory regions of coliphage H-19B: location of Shiga-like toxin and lysis genes suggest a role for phage functions in toxin release. Mol. Microbiol. 28:1255-1267[Medline]. |
| 62. | Nodwell, J. R., and J. Greenblatt. 1993. Recognition of boxA antiterminator RNA by the E. coli antitermination factors NusB and ribosomal protein S10. Cell 72:261-268[Medline]. |
| 62a. | Nudler, E. Personal communication. |
| 63. | Nudler, E., E. Avetissova, V. Markovtsov, and A. Goldfarb. 1996. Transcription processivity: protein-DNA interactions holding together the elongation complex. Science 273:211-217[Abstract]. |
| 64. |
Nudler, E.,
I. Gusarov,
E. Avetissova,
M. Kozlov, and A. Goldfarb.
1998.
Spatial organization of transcription elongation complex in Escherichia coli.
Science
281:424-428 |
| 65. | Nudler, E., A. Mustaev, E. Lukhtanov, and A. Goldfarb. 1997. The RNA-DNA hybrid maintains the register of transcription by preventing backtracking of RNA polymerase. Cell 89:33-41[Medline]. |
| 66. | Oberto, J., M. Clerget, M. Ditto, K. Cam, and R. A. Weisberg. 1993. Antitermination of early transcription in phage HK022. Absence of a phage-encoded antitermination factor. J. Mol. Biol. 229:368-381[Medline]. |
| 67. | Oberto, J., R. A. Weisberg, and M. E. Gottesman. 1989. Structure and function of the nun gene and the immunity region of the lambdoid phage HK022. J. Mol. Biol. 207:675-693[Medline]. |
| 68. | Obuchowski, M., A. Wegrzyn, A. Szalewska-Palasz, M. S. Thomas, and G. Wegrzyn. 1997. An RNA polymerase alpha subunit mutant impairs N-dependent transcriptional antitermination in Escherichia coli. Mol. Microbiol. 23:211-222[Medline]. |
| 69. | Ogawa, T., H. Masukata, and J. Tomizawa. 1988. Transcriptional regulation of early functions of bacteriophage phi 80. J. Mol. Biol. 202:551-563[Medline]. |
| 70. | Olson, E. R., E. L. Flamm, and D. I. Friedman. 1982. Analysis of nutR: a region of phage lambda required for antitermination of transcription. Cell 31:61-70[Medline]. |
| 71. |
Orlova, M.,
J. Newlands,
A. Das,
A. Goldfarb, and S. Borukhov.
1995.
Intrinsic transcript cleavage activity of RNA polymerase.
Proc. Natl. Acad. Sci. USA
92:4596-4600 |
| 72. |
Paton, A. W.,
J. C. Paton,
P. N. Goldwater,
M. W. Heuzenroeder, and P. A. Manning.
1993.
Sequence of a variant Shiga-like toxin type-I operon of Escherichia coli O111:H.
Gene
129:87-92[Medline].
|
| 73. | Patterson, T. A., Z. Zhang, T. Baker, L. L. Johnson, D. I. Friedman, and D. L. Court. 1994. Bacteriophage lambda N-dependent transcription antitermination. Competition for an RNA site may regulate antitermination. J. Mol. Biol. 236:217-228[Medline]. |
| 74. | Rees, W. A., S. E. Weitzel, A. Das, and P. H. von Hippel. 1997. Regulation of the elongation-termination decision at intrinsic terminators by antitermination protein N of phage lambda. J. Mol. Biol. 273:797-813[Medline]. |
| 75. |
Rees, W. A.,
S. E. Weitzel,
T. D. Yager,
A. Das, and P. H. von Hippel.
1996.
Bacteriophage lambda N protein alone can induce transcription antitermination in vitro.
Proc. Natl. Acad. Sci. USA
93:342-346 |
| 76. | Richardson, J. P., and J. Greenblatt. 1996. Control of RNA chain elongation and termination, p. 822-848. In F. C. Neidhardt, R. C. Curtiss III, J. L. Ingraham, E. C. C. Lin, K. B. Low, B. Magasanik, W. S. Reznikoff, M. Riley, M. Schaechter, and H. E. Umbarger (ed.), Escherichia coli and Salmonella: cellular and molecular biology. ASM Press, Washington, D.C. |
| 77. | Ring, B. Z., W. S. Yarnell, and J. W. Roberts. 1996. Function of E. coli RNA polymerase sigma factor sigma 70 in promoter-proximal pausing. Cell 86:485-493[Medline]. |
| 78. | Robert, J., S. B. Sloan, R. A. Weisberg, M. E. Gottesman, R. Robledo, and D. Harbrecht. 1987. The remarkable specificity of a new transcription termination factor suggests that the mechanisms of termination and antitermination are similar. Cell 51:483-492[Medline]. |
| 79. | Roberts, J. W. 1969. Termination factor for RNA synthesis. Nature 224:1168-1174[Medline]. |
| 80. | Roberts, J. W. 1996. Transcription termination and its control, p. 27-45. In E. C. C. Lin, and A. S. Lynch (ed.), Regulation of gene expression in Escherichia coli. Chapman Hall, New York, N.Y. |
| 81. | Robledo, R., B. L. Atkinson, and M. E. Gottesman. 1991. Escherichia coli mutations that block transcription termination by phage HK022 Nun protein. J. Mol. Biol. 220:613-619[Medline]. |
| 82. | Rosenberg, M., D. L. Court, H. Shimatake, C. Brady, and D. L. Wulff. 1978. The relationship between function and DNA sequence in an intercistronic regulatory region in phage lambda. Nature 272:414-423[Medline]. |
| 83. |
Salstrom, J. S., and W. Szybalski.
1978.
Coliphage lambda nutL : a unique class of mutants defective in the site of gene N product utilization for antitermination of leftward transcription.
J. Mol. Biol.
124:195-221[Medline].
|
| 84. | Schauer, A. T., D. L. Carver, B. Bigelow, L. S. Baron, and D. I. Friedman. 1987. Lambda N antitermination system: functional analysis of phage interactions with the host NusA protein. J. Mol. Biol. 194:679-690[Medline]. |
| 85. | Schauer, A. T., S. W. Cheng, C. Zheng, L. St. Pierre, D. Alessi, D. L. Hidayetoglu, N. Costantino, D. L. Court, and D. I. Friedman. 1996. The alpha subunit of RNA polymerase and transcription antitermination. Mol. Microbiol. 21:839-851[Medline]. |
| 86. | Schmidt, M. C., and M. J. Chamberlin. 1984. Amplification and isolation of Escherichia coli nusA protein and studies of its effects on in vitro RNA chain elongation. Biochemistry 23:197-203[Medline]. |
| 86a. |
Sharrock, R. A.,
R. L. Gourse, and M. Nomura.
1985.
Defective antitermination of rRNA transcription and derepression of rRNA and tRNA synthesis in the nusB5 mutant of Escherichia coli.
Proc. Natl. Acad. Sci. USA
82:5275-5279 |
| 87. | Sidorenkov, I., N. Komissarova, and M. Kashlev. 1998. Crucial role of the RNA:DNA hybrid in the processivity of transcription. Mol. Cell 2:55-64[Medline]. |
| 88. |
Sloan, S. B., and R. A. Weisberg.
1993.
Use of a gene encoding a suppressor tRNA as a reporter of transcription: analyzing the action of the Nun protein of bacteriophage HK022.
Proc. Natl. Acad. Sci. USA
90:9842-9846 |
| 89. |
Squires, C. L.,
J. Greenblatt,
J. Li, and C. Condon.
1993.
Ribosomal RNA antitermination in vitro: requirement for Nus factors and one or more unidentified cellular components.
Proc. Natl. Acad. Sci. USA
90:970-974 |
| 90. |
Steinmetz, E. J.,
C. A. Brennan, and T. Platt.
1990.
A short intervening structure can block rho factor helicase action at a distance.
J. Biol. Chem.
265:18408-18413 |
| 91. | Stevens, M. P., B. R. Clarke, and I. S. Roberts. 1997. Regulation of the Escherichia coli K5 capsule gene cluster by transcription antitermination. Mol. Microbiol. 24:1001-1012[Medline]. |
| 92. | Su, L., J. T. Radek, K. Hallenga, P. Hermanto, G. Chan, L. A. Labeots, and M. A. Weiss. 1997. RNA recognition by a bent alpha-helix regulates transcriptional antitermination in phage lambda. Biochemistry 36:12722-12732[Medline]. |
| 93. | Sullivan, S. L., and M. E. Gottesman. 1992. Requirement for E. coli NusG protein in factor-dependent transcription termination. Cell 68:989-994[Medline]. |
| 94. | Sunshine, M., and E. Six. 1976. Relief of P2 bacteriophage amber mutant polarity by the satellite bacteriophage P4. J. Mol. Biol. 106:673-682[Medline]. |
| 95. |
Surratt, C. K.,
S. C. Milan, and M. J. Chamberlin.
1991.
Spontaneous cleavage of RNA in ternary complexes of Escherichia coli RNA polymerase and its significance for the mechanism of transcription.
Proc. Natl. Acad. Sci. USA
88:7983-7987 |
| 96. | Uptain, S. M., C. M. Kane, and M. J. Chamberlin. 1997. Basic mechanisms of transcript elongation and its regulation. Annu. Rev. Biochem. 66:117-172[Medline]. |
| 97. |
Vogel, U., and K. F. Jensen.
1995.
Effects of the antiterminator BoxA on transcription elongation kinetics and ppGpp inhibition of transcription elongation in Escherichia coli.
J. Biol. Chem.
270:18335-18340 |
| 98. |
Vogel, U., and K. F. Jensen.
1997.
NusA is required for ribosomal antitermination and for modulation of the transcription elongation rate of both antiterminated RNA and mRNA.
J. Biol. Chem.
272:12265-12271 |
| 99. |
von Hippel, P. H.
1998.
An integrated model of the transcription complex in elongation, termination, and editing.
Science
281:660-665 |
| 100. |
Watnick, R. S., and M. E. Gottesman.
1998.
Escherichia coli NusA is required for efficient RNA binding by phage HK022 nun protein.
Proc. Natl. Acad. Sci. USA
95:1546-1551 |
| 101. | Weiss, M. A. 1998. RNA-mediated signaling in transcription. Nat. Struct. Biol. 5:329-333[Medline]. |
| 102. | Yang, X. J., J. A. Goliger, and J. W. Roberts. 1989. Specificity and mechanism of antitermination by Q proteins of bacteriophages lambda and 82. J. Mol. Biol. 210:453-460[Medline]. |
| 103. |
Yang, X. J., and J. W. Roberts.
1989.
Gene Q antiterminator proteins of Escherichia coli phages 82 and lambda suppress pausing by RNA polymerase at a rho-dependent terminator and at other sites.
Proc. Natl. Acad. Sci. USA
86:5301-5305 |
| 104. | Yanofsky, C., K. V. Konan, and J. P. Sarsero. 1996. Some novel transcription attenuation mechanisms used by bacteria. Biochimie 78:1017-1024[Medline]. |
| 105. | Yarnell, W. S., and J. W. Roberts. 1992. The phage lambda gene Q transcription antiterminator binds DNA in the late gene promoter as it modifies RNA polymerase. Cell 69:1181-1189[Medline]. |
This article has been cited by other articles:
| ||||||||||
),
intermolecular hydrogen bonding or electrostatic interactions
(<-----), intermolecular hydrophobic or van der
Waals interactions (
), intramolecular hydrogen bonds
(----) and Watson-Crick base pairs
(|||||) are indicated. Cytosine-11 is extruded from the loop
(see text). Note that the amino-terminal amino acid residue in the
complex corresponds to Asn-14 in the complete protein (Fig. 