Key points are not available for this paper at this time.
Expression of the trpEDCFBA operon is regulated at both the transcriptional and translational levels by thetrp RNA-binding attenuation protein (TRAP) ofBacillus subtilis. When cells contain sufficient levels of tryptophan to activate TRAP, the protein binds to trpoperon transcripts as they are being synthesized, most often causing transcription termination. However, termination is never 100% efficient, and transcripts that escape termination are subject to translational control. We determined that TRAP-mediated translational control of trpE can occur via a novel RNA conformational switch mechanism. When TRAP binds to the 5′-untranslated leader segment of a trp operon read-through transcript, it can disrupt a large secondary structure containing a portion of the TRAP binding target. This promotes refolding of the RNA such that thetrpE Shine-Dalgarno sequence, located more than 100 nucleotides downstream from the TRAP binding site, becomes sequestered in a stable RNA hairpin. Results from cell-free translation, ribosome toeprint, and RNA structure mapping experiments demonstrate that formation of this structure reduces TrpE synthesis by blocking ribosome access to the trpE ribosome binding site. The role of the Shine-Dalgarno blocking hairpin in controlling translation oftrpE was confirmed by examining the effect of multiple nucleotide substitutions that abolish the structure without altering the Shine-Dalgarno sequence itself. The possibility of protein-mediated RNA refolding as a general mechanism in controlling gene expression is discussed. Expression of the trpEDCFBA operon is regulated at both the transcriptional and translational levels by thetrp RNA-binding attenuation protein (TRAP) ofBacillus subtilis. When cells contain sufficient levels of tryptophan to activate TRAP, the protein binds to trpoperon transcripts as they are being synthesized, most often causing transcription termination. However, termination is never 100% efficient, and transcripts that escape termination are subject to translational control. We determined that TRAP-mediated translational control of trpE can occur via a novel RNA conformational switch mechanism. When TRAP binds to the 5′-untranslated leader segment of a trp operon read-through transcript, it can disrupt a large secondary structure containing a portion of the TRAP binding target. This promotes refolding of the RNA such that thetrpE Shine-Dalgarno sequence, located more than 100 nucleotides downstream from the TRAP binding site, becomes sequestered in a stable RNA hairpin. Results from cell-free translation, ribosome toeprint, and RNA structure mapping experiments demonstrate that formation of this structure reduces TrpE synthesis by blocking ribosome access to the trpE ribosome binding site. The role of the Shine-Dalgarno blocking hairpin in controlling translation oftrpE was confirmed by examining the effect of multiple nucleotide substitutions that abolish the structure without altering the Shine-Dalgarno sequence itself. The possibility of protein-mediated RNA refolding as a general mechanism in controlling gene expression is discussed. Studies on the regulation of protein synthesis have shown that the RNA secondary structural features present in the 5′-UTR 1The abbreviations used are: UTRuntranslated regionSDShine-DalgarnoTRAPtrp RNA-binding attenuation proteinDMSdimethyl sulfateCMCT1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide methop-toluenesulfonate. dramatically influence translation initiation in both prokaryotic and eukaryotic organisms (for recent reviews see Refs. 1de Smit M.H. van Duin J. Prog. Nucleic Acids Res. Mol. Biol. 1990; 38: 1-35Crossref PubMed Scopus (163) Google Scholar, 2Kozak M. Annu. Rev. Cell Biol. 1992; 8: 197-225Crossref PubMed Scopus (416) Google Scholar, 3Lindahl L. Hinnebusch A. Curr. Opin. Genet. Dev. 1992; 2: 720-726Crossref PubMed Scopus (18) Google Scholar, 4Pantopoulos K. Johansson H.E. Hentze M.W. Prog. Nucleic Acids Res. Mol. Biol. 1994; 48: 181-238Crossref PubMed Scopus (16) Google Scholar, 5Zengel J.M. Lindahl L. Prog. Nucleic Acids Res. Mol. Biol. 1994; 47: 331-370Crossref PubMed Scopus (202) Google Scholar, 6Klaff P. Riesner D. Steger G. Plant Mol. Biol. 1996; 32: 89-106Crossref PubMed Scopus (49) Google Scholar, 7Jackson R.J. Wickens M. Curr. Opin. Genet. Dev. 1997; 7: 233-241Crossref PubMed Scopus (69) Google Scholar). In prokaryotic mRNAs, a conserved stretch of 4–6 nucleotides called the Shine-Dalgarno (SD) sequence is usually found 4–11 nucleotides upstream of the initiation codon. The SD sequence base pairs with the 16 S rRNA present in the 30 S ribosomal subunit and thereby correctly positions the initiation codon in the ribosome (8Steitz J.A. Jakes K. Proc. Natl. Acad. Sci. U. S. A. 1975; 72: 4734-4738Crossref PubMed Scopus (506) Google Scholar, 9Ma C.K. Kolesnikow T. Rayner J.C. Simons E.L. Yim H. Simons R.W. Mol. Microbiol. 1994; 14: 1033-1047Crossref PubMed Scopus (35) Google Scholar). Translational control mechanisms have in that blocking the SD sequence by RNA secondary structure C.K. Kolesnikow T. Rayner J.C. Simons E.L. Yim H. Simons R.W. Mol. Microbiol. 1994; 14: 1033-1047Crossref PubMed Scopus (35) Google Scholar, P. Smit M. M. J. van Duin J. M. J. Mol. Biol. PubMed Scopus Google Scholar, J. PubMed Google Scholar, van Duin J. Proc. Natl. Acad. Sci. U. S. A. 1997; PubMed Scopus Google by a protein Nucleic Acids Res. PubMed Scopus Google Scholar, S. L. L. J. J. L. Nucleic Acids Res. 1990; PubMed Scopus (18) Google Scholar, M. A. van P. J. PubMed Google Scholar, H. P. J. 1997; PubMed Google Scholar). In the translational control mechanisms that occur by formation of SD blocking formation of the structure is and protein Shine-Dalgarno trp RNA-binding attenuation protein methop-toluenesulfonate. Expression of the tryptophan is regulated in to in the of tryptophan at both the transcriptional and translational levels (for a recent see P. Mol. Microbiol. 1997; PubMed Scopus Google Scholar). of the trp are in the trpEDCFBA of thetrp operon is regulated by attenuation mechanism in trp RNA-binding attenuation protein (TRAP) binds to and H. J. PubMed Google Scholar, D. J. PubMed Google Scholar, P. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, J. P. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, P. J. Biol. 1994; PubMed Google Scholar, J. M. T. P. PubMed Scopus Google Scholar, P. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, P. J. PubMed Google Scholar). TRAP binding to the in the trp leader formation of RNA secondary the thereby formation of and causing termination of transcription RNA thetrp structural In the of TRAP formation of the formation of the in transcriptional read-through the In to transcription of thetrp TRAP translation in that TRAP is trpE translation D. J. PubMed Google Scholar, P. J. PubMed Google Scholar). RNA structure of the trpoperon read-through that the most stable of the leader RNA segment contain a large secondary structure that a portion of the TRAP binding in the of the was that TRAP binding to disrupt the large secondary structure and refolding of the leader RNA such that the sequence sequestered in RNA hairpin D. J. PubMed Google Scholar, P. J. PubMed Google Scholar). was shown that multiple nucleotide substitutions to the SD blocking without altering the SD sequence the of TRAP to TrpE synthesis in P. J. PubMed Google Scholar). the of TRAP to the operon read-through transcripts the translational control of that was D. J. PubMed Google Scholar, P. J. PubMed Google Scholar). The trp is a of a operon J. J. 1990; PubMed Google Scholar). Expression of is regulated by a translational control mechanism in TRAP can to and that and ribosome binding site. TRAP binding to synthesis by blocking ribosome access to ribosome binding M. A. van P. J. PubMed Google Scholar, H. P. J. 1997; PubMed Google Scholar). The structure of TRAP with that TRAP is of in a with of tryptophan J. M. T. P. PubMed Scopus Google Scholar, T. J. P. J. Mol. Biol. 1994; PubMed Scopus Google Scholar). The RNA binding of TRAP of that the of the TRAP This that a mechanism in binds to thereby the RNA the of the TRAP M. K. P. J. Mol. Biol. 1997; PubMed Scopus Google Scholar). In the present experiments in to the mechanism TRAP-mediated translation control of cell-free translation and RNA structural demonstrate that TRAP binding to trpoperon read-through transcripts in refolding of the trp leader such that the trpE SD sequence, is located more than 100 nucleotides downstream from the TRAP binding site, becomes sequestered in a stable RNA hairpin. found that formation of this SD blocking hairpin TrpE synthesis by blocking ribosome access to the binding site. the trp and leader P. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). The trp leader that the trpE SD blocking RNA hairpin without the trpE SD sequence P. J. PubMed Google Scholar). was by the containing the from of the of L. H. Scopus Google Scholar). was by the containing the trp operon and leader as as the structural from the of The the and the of This was by the from containing the and the of as as the from containing the of trpE and the the of the was in the as that the containing the from was used in of the The used the of translational was P. J. PubMed Google Scholar). The and contain translational by the trp leader from the of The and and the of was by J. J. PubMed Google was was confirmed by the of by J. H. J. 1975; PubMed Google Scholar). The trp and contain both operon in the and translational control of the trp with a a leader in TrpE protein was the S. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google such that expression of trpE is control of RNA of TrpE was by a S. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). in J. Proc. Natl. Acad. Sci. U. S. A. PubMed Google containing and in the of was in by with and in of in Scholar). with of was and the at to the of of was as in Scholar). TRAP was as P. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). of a H. P. J. 1997; PubMed Google Scholar). The RNA used in this was the and with as of the of of of transcript, and of and the was at to the of the of TRAP used in are in the at 30 by the of of H. P. J. 1997; PubMed Google Scholar). at and a protein with a and the of RNA secondary the and trp the J.A. M. 1990; PubMed Scopus Google Scholar). on the experiments to the of the of stable RNA secondary transcripts used in this with the in transcription trp blocking hairpin as of to nucleotides to the of trp operon of in of TRAP, and in The was at to formation and to the and the to the of of was at with by in of by the of of The 30 S ribosomal subunit a H. P. J. 1997; PubMed Google that was used The transcripts and used in the are with the the and The transcripts used in this the in and as of and to the of that multiple in that the of secondary in RNA RNA with of TRAP, of and in P. J. Biol. 1994; PubMed Google Scholar). to at at of of was and the at with and the RNA was by as P. J. Biol. 1994; PubMed Google Scholar). to at to the of of to the a at and the RNA was as S. L. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). was by and at 30 and the RNA was as RNA and in of RNA and of in to and on the of was by of at by the of of the and in that TRAP can translation the structural gene of the D. J. PubMed Google Scholar, P. J. PubMed Google Scholar). was shown that containing in thetrp leader that to the SD blocking hairpin without altering the SD sequence the of TRAP to TrpE synthesis P. J. PubMed Google Scholar). in translational that by the trp leader and expression was in the and of We expression in the in the of tryptophan The effect of tryptophan on expression of can from the was that this both transcriptional and translational experiments with the In this the was than that the the of expression of the in the of tryptophan to the of TRAP-mediated translational control. The of is in with in D. J. PubMed Google Scholar, P. J. PubMed Google in shown are of more experiments The shown are of more experiments in a the translational regulation oftrpE cell-free translation in a was used to TRAP binding to trp operon leader RNA TrpE The in transcripts used in this the trp leader and the in control the of of TrpE protein When used the cell-free translation a protein that was the TrpE in translation without the of trpE RNA When the was with of TRAP to the of the of the translation a in TrpE translation was and When the was the of of TRAP to the translation in a in TrpE synthesis and that it was to the control in TRAP is in the of tryptophan is TrpE When with demonstrate that TRAP binding to the located nucleotides and of the trp leader in a of TrpE a of the trpE translational the RNA to in the leader segment of trp operon read-through transcripts J.A. M. 1990; PubMed Scopus Google Scholar). In this nucleotides to the of The most stable RNA secondary structure to in the trp leader is shown in the that the TRAP binding are in the of the base of this the are to the of the TRAP binding that TRAP binding disrupt the base of this We the RNA to TRAP was to the from positions of the trp We determined the to nucleotides and and and that in this nucleotides from the In secondary to in the downstream from the TRAP binding of of the present at the of the structure structure the trpE SD sequence in the of the that TRAP is to the transcript, the nucleotides that the of the SD blocking hairpin with a segment of the TRAP binding the a that the regulation of TrpE In this binding of TRAP to located nucleotides and operon read-through transcripts disrupt the structure to in the This thetrp leader to such that the nucleotides that with the TRAP binding to in the formation of RNA secondary structure that the trpE SD sequence, to a in TrpE synthesis by ribosome access to thetrpE ribosome binding site. TRAP binding trpE translation by altering the of the more than 100 nucleotides downstream from the of the TRAP binding site. TRAP binding promotes formation of the trpE SD blocking hairpin experiments in containing the trp The of a protein a stable RNA secondary structure by in a at a to the of the protein at a the of the RNA that in to the base of the that the is a stable structure and that it is by the binding of TRAP 30 S ribosomal In a at was in the of TRAP in This to the of the TRAP and is in with the TRAP binding that at RNA structural at positions and TRAP was to the to positions at the base of the SD blocking hairpin structure TRAP was to the In the of TRAP RNA at positions and to positions the base of the secondary structure to in the trp leader of read-through transcripts TRAP was to the RNA was at the secondary structure this is it is that it can in the of TRAP and that it ribosome binding it was that the of the to the base of the SD blocking hairpin in the of TRAP, the that they that the are in TRAP is it is that the structure shown in is demonstrate that TRAP binding in refolding of trp operon read-through the structure of the trpE SD it is that the SD sequence of with the of the 16 S rRNA present in 30 S ribosomal Smit M.H. van Duin J. Prog. Nucleic Acids Res. Mol. Biol. 1990; 38: 1-35Crossref PubMed Scopus (163) Google Scholar, J.A. Jakes K. Proc. Natl. Acad. Sci. U. S. A. 1975; 72: 4734-4738Crossref PubMed Scopus (506) Google that formation of the SD blocking hairpin with ribosome this a trp leader 30 S ribosomal In the of TRAP, a nucleotides downstream from the nucleotide in the initiation codon the that was the ribosome H. P. J. 1997; PubMed Google Scholar). In to the ribosome toeprint, the the of is that binding of 30 S ribosomal the large RNA secondary structure shown in A. We in TRAP binding with the of to to the trpE When TRAP was to to the trp leader to the of 30 S ribosomal the ribosome was as the of TRAP to formation of the SD blocking hairpin with ribosome in the at positions and and that TRAP and ribosome binding are in with that are to to a containing the SD blocking at a When 30 S ribosomal to the of TRAP, the of the ribosomal was the of the at positions and dramatically and that of the 16 S rRNA with the SD sequence with the of TRAP to formation of the SD blocking with trpE translational control The are with thetrpE translational control in TRAP binding operon read-through transcripts promotes refolding of the trp leader RNA such that a secondary structure from with the more the RNA conformational switch the structure of trp leader read-through with and in the of trpoperon read-through transcripts to The of by the that was used in the of nucleotides to a nucleotide than the in the the of of thetrp leader RNA secondary that in the of The of the structure mapping experiments are shown in and in a control that are by RNA secondary structure to experiments in the of TRAP without in and of Shine-Dalgarno blocking hairpin structure mapping This is from the in of by the are shown with the of the to the of the of RNA the are of by the are shown by The and most in the structure of the SD blocking hairpin. In the of TRAP, of the located in the SD RNA segment positions and by was TRAP was to the transcript, that are in the of TRAP in and We at TRAP was to the transcript, that this is TRAP is to the that is in the of the SD blocking hairpin In the of that this is in the of TRAP and that it can TRAP is to the the that and are TRAP is to the in of the are with the RNA and The with are in with the and the and When TRAP was to the transcript, was at positions and that nucleotides and The of at positions and that nucleotides that to the and of the of the SD blocking The dramatically TRAP was to the The in that was the SD that this RNA segment is in the of TRAP However, was positions and to positions the base of the structure to TRAP is more the structure of the RNA thetrpE SD sequence in the and of TRAP, experiments with and of and of the are and at the and and are to as The the In the of TRAP, of the and and by that and was and as this RNA segment is TRAP is of the at positions and was TRAP was to thetrp that nucleotides and In levels of at and that TRAP was The of that this RNA segment is TRAP is the at is a SD blocking hairpin and that with the of the are with the shown in and that the that was TRAP was to the trp leader Results from the experiments with the structural mapping experiments and the structure of the SD blocking hairpin In the of TRAP, at positions and that However, the of of and with the that in a of that they can in the of TRAP The of of the and and that nucleotides In the of TRAP, at and that nucleotides that are present the and and the of the SD blocking hairpin We of and that nucleotides can TRAP is However, the and are with being and We a that to to is it is that this is RNA structural by a secondary in the the at positions and are of the SD blocking hairpin and When with the in translation the RNA structural demonstrate that TRAP binding to the trp leader read-through is formation of the trpE SD blocking and that formation of this structure TrpE synthesis by with ribosome binding to the confirmed P. J. PubMed Google that the in the the of TRAP to TrpE of the that of the SD blocking a secondary structure that thetrpE SD sequence in the of the hairpin the in translational control to the of the SD blocking hairpin to RNA structural on the We found that the nucleotide substitutions the RNA structural positions and that the large secondary structure in the of TRAP and that TRAP binding the structure However, RNA that to the base of the SD blocking hairpin. a RNA structural at in the and of as a structure can in the of the trpE SD sequence in the in this formation of the structure was on TRAP We a 30 S ribosomal the was the transcript, a ribosomal We found that TRAP binding the of the ribosome the was than was with the with This that the RNA structure a effect on ribosome binding with the SD blocking TRAP binding the of 30 S ribosomal to with the trpE SD The that TRAP binding to the the RNA structure the trpE SD this and structure mapping experiments on the trp The as the SD blocking hairpin was present in the found that TRAP binding effect on the structure of the downstream of However, as was in the RNA structural TRAP binding the RNA and that TRAP binding the large RNA secondary structure in the mapping experiments with and with the the in and structure mapping of the are with the in that TRAP-mediated translational control was in the P. J. PubMed Google Scholar). Expression of the trpEDCFBA operon is regulated by TRAP at both the transcriptional and translational TRAP is to expression at the of translation P. Mol. Microbiol. 1997; PubMed Scopus Google Scholar). it is that TRAP-mediated formation of the SD blocking hairpin is TrpE RNA refolding this structure to in When cells are of tryptophan TRAP and most to the as it is being In most this termination in the leader in RNA escape termination TRAP binding transcription termination is never 100% In TRAP to transcription of thetrpE SD sequence in to termination. of in a read-through that RNA refolding to thetrpE SD sequence in the SD blocking hairpin. is more that the TRAP-mediated RNA refolding mechanism that read-through transcripts occur in cells tryptophan a of TRAP in transcriptional The leader of transcripts to the structure shown in in TrpE by synthesis a sufficient of tryptophan to activate TRAP to the trp leader and RNA refolding and formation of the SD blocking to a in trpE that of the operon by nucleotides and However, in this the are by L. H. Scopus Google Scholar). This gene that translational a role operon TRAP-mediated formation of thetrpE SD blocking hairpin translation of the that synthesis is regulated by formation of thetrpE SD blocking hairpin. and P. is that translational to of the trp operon transcript, a of ribosome on the in In it is that translational oftrpE to transcriptional by access of termination of mechanisms to control trpoperon the of in demonstrate that TRAP the to TrpE synthesis by RNA cell-free translation experiments that levels of TRAP in a in TrpE synthesis that TRAP binding to nucleotides of trp operon read-through transcripts disrupt the base of a RNA structure by of the that of the that the TRAP binding are present in the of the the are to and it is that TRAP is RNA P. J. D. J. 1996; PubMed Scopus Google it is that of the structure by a mechanism in TRAP binds to the and with the present in the secondary to of the that TRAP was the nucleotides positions and to in the formation of a RNA hairpin that the trpE SD sequence in the of the structure and thereby ribosome access to the binding this mechanism at of the in TrpE synthesis that was in D. J. PubMed Google Scholar, P. J. PubMed Google and in Results from experiments that TRAP binding refolding of trp leader transcripts and that the structure ribosome binding from RNA structure mapping experiments demonstrate that the SD blocking hairpin the SD sequence in the of the and in the structure mapping the with and However, occur at and in to nucleotides in RNA can the in a RNA segment that is to RNA as as in in the nucleotides are J. Biol. PubMed Google Scholar). from are translational containing in the trp leader to the SD blocking hairpin without altering the SD sequence was P. J. PubMed Google Scholar). was determined that the of TRAP to trpE translation P. J. PubMed Google Scholar). RNA structural the structural this of the SD blocking a structure can in the of thetrpE SD sequence and the that formation of this structure in the of TRAP, found that TRAP binding in a in ribosome binding to of the the translational regulation that was in as a of translational control D. J. PubMed Google P. J. PubMed Google Scholar). In the to translation of transcripts in to the to the synthesis of and by the synthesis of that are This to the the trp operon of subtilis. the the to tryptophan is a of TrpE and J. PubMed Google blocking translation oftrpE a sufficient of tryptophan is present in the a to tryptophan This more of in the synthesis of and D. J.A. and and D. Scholar, J.A. and and D. Scholar). the of TrpE synthesis is to of TrpE and is mechanism the to the of tryptophan in the The of translational control mechanisms the of protein in translation of is by binding of a protein to the SD In the RNA-binding protein ribosome access to the ribosome binding Nucleic Acids Res. PubMed Scopus Google Scholar, S. L. L. J. J. L. Nucleic Acids Res. 1990; PubMed Scopus (18) Google Scholar, H. P. J. 1997; PubMed Google Scholar). in RNA secondary are translation by the SD sequence (for see Refs. 1de Smit M.H. van Duin J. Prog. Nucleic Acids Res. Mol. Biol. 1990; 38: 1-35Crossref PubMed Scopus (163) Google Scholar, 3Lindahl L. Hinnebusch A. Curr. Opin. Genet. Dev. 1992; 2: 720-726Crossref PubMed Scopus (18) Google Scholar, 5Zengel J.M. Lindahl L. Prog. Nucleic Acids Res. Mol. Biol. 1994; 47: 331-370Crossref PubMed Scopus (202) Google Scholar, 9Ma C.K. Kolesnikow T. Rayner J.C. Simons E.L. Yim H. Simons R.W. Mol. Microbiol. 1994; 14: 1033-1047Crossref PubMed Scopus (35) Google Scholar, and van Duin J. Proc. Natl. Acad. Sci. U. S. A. 1997; PubMed Scopus Google Scholar). translation of the C.K. Kolesnikow T. Rayner J.C. Simons E.L. Yim H. Simons R.W. Mol. Microbiol. 1994; 14: 1033-1047Crossref PubMed Scopus (35) Google and the gene van Duin J. Proc. Natl. Acad. Sci. U. S. A. 1997; PubMed Scopus Google is by formation of RNA that ribosome in both of mechanisms the of RNA than RNA-binding are the In it was shown that expression of the gene is regulated at the translational by a ribosome binding and sequence and of the it that a protein is in this J. PubMed Google Scholar). translational control mechanism was the In this RNA hairpin that a portion of SD sequence is the protein binds upstream of the secondary protein as a translational by altering the of the RNA the SD sequence such that can access to the ribosome binding S. L. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, PubMed Scopus Google Scholar). that translation of the operon is regulated by a mechanism in binding of to the leader segment of the operon promotes formation of RNA structure that ribosome a in the RNA in the of However, to this the binding is J.M. Lindahl L. Prog. Nucleic Acids Res. Mol. Biol. 1994; 47: 331-370Crossref PubMed Scopus (202) Google Scholar). translational mechanism the operon that is to the mechanism that the trp operon T. M. J. PubMed Scopus Google Scholar). In this it is that binding of the to the operon leader promotes of the SD sequence in a stable secondary However, structural have to the structural switch J. Biol. PubMed Google Scholar). the trpE translational control mechanism is the in RNA-binding protein was found to refolding of the to a SD sequence, it is to that this to a mechanism by it is that this in in the of trpE of the SD sequence is more than 100 nucleotides downstream from the of the TRAP binding site. is to that protein-mediated RNA refolding eukaryotic translation as initiation of the of eukaryotic via a ribosomal mechanism M. Annu. Rev. Cell Biol. 1992; 8: 197-225Crossref PubMed Scopus (416) Google Scholar). of the by eukaryotic initiation of a S ribosomal and of RNA secondary of S is on the 5′-UTR secondary is that secondary structure in the 5′-UTR translation initiation and in Nucleic Acids Res. 1996; PubMed Scopus Google Scholar, D. Nucleic Acids Res. 1997; PubMed Scopus Google Scholar). and translation by a initiation mechanism A. R.J. Genet. 1994; Scholar). initiation is by the binding of to ribosome the The ribosome are in conserved are D. L. 1997; PubMed Scopus Google Scholar). in translation regulated by protein-mediated refolding of RNA by altering the RNA structure ribosome by with the ribosomal mechanism. is that protein-mediated RNA refolding altering the of prokaryotic and eukaryotic by by to We 30 S ribosomal and We and of the
Du et al. (Sat,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: