Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 297 (5588): 1864-1867

Copyright © 2002 by the American Association for the Advancement of Science

Instruction of Translating Ribosome by Nascent Peptide

Feng Gong, Charles Yanofsky*

Expression of the tryptophanase operon of Escherichia coli is regulated by catabolite repression and tryptophan-induced transcription antitermination. An induction site activated by L-tryptophan is created in the translating ribosome during synthesis of TnaC, the 24-residue leader peptide. Replacing the tnaC stop codon with a tryptophan codon allows tryptophan-charged tryptophan transfer RNA to substitute for tryptophan as inducer. This suggests that the ribosomal A site occupied by the tryptophanyl moiety of the charged transfer RNA is the site of induction. The location of tryptophan-12 of nascent TnaC in the peptide exit tunnel was crucial for induction. These results show that a nascent peptide sequence can influence translation continuation and termination within a translating ribosome.

Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
*   To whom correspondence should be addressed. E-mail: yanofsky{at}

Interactions of the TnaC nascent peptide with rRNA in the exit tunnel enable the ribosome to respond to free tryptophan.
A. K. Martinez, E. Gordon, A. Sengupta, N. Shirole, D. Klepacki, B. Martinez-Garriga, L. M. Brown, M. J. Benedik, C. Yanofsky, A. S. Mankin, et al. (2014)
Nucleic Acids Res. 42, 1245-1256
   Abstract »    Full Text »    PDF »
Mutations in the Escherichia coli Ribosomal Protein L22 Selectively Suppress the Expression of a Secreted Bacterial Virulence Factor.
M.-N. F. Yap and H. D. Bernstein (2013)
J. Bacteriol. 195, 2991-2999
   Abstract »    Full Text »    PDF »
Divergent Protein Motifs Direct Elongation Factor P-Mediated Translational Regulation in Salmonella enterica and Escherichia coli.
S. J. Hersch, M. Wang, S. B. Zou, K.-M. Moon, L. J. Foster, M. Ibba, and W. W. Navarre (2013)
mBio 4, e00180-13
   Abstract »    Full Text »    PDF »
Nascent peptides that block protein synthesis in bacteria.
C. J. Woolstenhulme, S. Parajuli, D. W. Healey, D. P. Valverde, E. N. Petersen, A. L. Starosta, N. R. Guydosh, W. E. Johnson, D. N. Wilson, and A. R. Buskirk (2013)
PNAS 110, E878-E887
   Abstract »    Full Text »    PDF »
Crucial elements that maintain the interactions between the regulatory TnaC peptide and the ribosome exit tunnel responsible for Trp inhibition of ribosome function.
A. K. Martinez, N. H. Shirole, S. Murakami, M. J. Benedik, M. S. Sachs, and L. R. Cruz-Vera (2012)
Nucleic Acids Res. 40, 2247-2257
   Abstract »    Full Text »    PDF »
Polytopic membrane protein folding at L17 in the ribosome tunnel initiates cyclical changes at the translocon.
P.-J. Lin, C. G. Jongsma, M. R. Pool, and A. E. Johnson (2011)
J. Cell Biol. 195, 55-70
   Abstract »    Full Text »    PDF »
CsrA and TnaB Coregulate Tryptophanase Activity To Promote Exotoxin-Induced Killing of Caenorhabditis elegansby Enteropathogenic Escherichia coli.
S. Bhatt, A. Anyanful, and D. Kalman (2011)
J. Bacteriol. 193, 4516-4522
   Abstract »    Full Text »    PDF »
Role of antibiotic ligand in nascent peptide-dependent ribosome stalling.
N. Vazquez-Laslop, D. Klepacki, D. C. Mulhearn, H. Ramu, O. Krasnykh, S. Franzblau, and A. S. Mankin (2011)
PNAS 108, 10496-10501
   Abstract »    Full Text »    PDF »
S-Adenosyl-L-methionine Induces Compaction of Nascent Peptide Chain inside the Ribosomal Exit Tunnel upon Translation Arrest in the Arabidopsis CGS1 Gene.
N. Onoue, Y. Yamashita, N. Nagao, D. B. Goto, H. Onouchi, and S. Naito (2011)
J. Biol. Chem. 286, 14903-14912
   Abstract »    Full Text »    PDF »
Picky nascent peptides do not talk to foreign ribosomes.
N. Vazquez-Laslop and A. S. Mankin (2011)
PNAS 108, 5931-5932
   Full Text »    PDF »
Recruitment of a species-specific translational arrest module to monitor different cellular processes.
S. Chiba, T. Kanamori, T. Ueda, Y. Akiyama, K. Pogliano, and K. Ito (2011)
PNAS 108, 6073-6078
   Abstract »    Full Text »    PDF »
Two groups of phenylalanine biosynthetic operon leader peptides genes: a high level of apparently incidental frameshifting in decoding Escherichia coli pheL.
O. L. Gurvich, S. J. Nasvall, P. V. Baranov, G. R. Bjork, and J. F. Atkins (2011)
Nucleic Acids Res. 39, 3079-3092
   Abstract »    Full Text »    PDF »
The key function of a conserved and modified rRNA residue in the ribosomal response to the nascent peptide.
N. Vazquez-Laslop, H. Ramu, D. Klepacki, K. Kannan, and A. S. Mankin (2010)
EMBO J. 29, 3108-3117
   Abstract »    Full Text »    PDF »
Production of Indole from L-Tryptophan and Effects of These Compounds on Biofilm Formation by Fusobacterium nucleatum ATCC 25586.
T. Sasaki-Imamura, A. Yano, and Y. Yoshida (2010)
Appl. Envir. Microbiol. 76, 4260-4268
   Abstract »    Full Text »    PDF »
Genetic Identification of Nascent Peptides That Induce Ribosome Stalling.
D. R. Tanner, D. A. Cariello, C. J. Woolstenhulme, M. A. Broadbent, and A. R. Buskirk (2009)
J. Biol. Chem. 284, 34809-34818
   Abstract »    Full Text »    PDF »
Nascent Proteins Caught in the Act.
M. Kampmann and G. Blobel (2009)
Science 326, 1352-1353
   Abstract »    Full Text »    PDF »
Structural Insight into Nascent Polypeptide Chain-Mediated Translational Stalling.
B. Seidelt, C. A. Innis, D. N. Wilson, M. Gartmann, J.-P. Armache, E. Villa, L. G. Trabuco, T. Becker, T. Mielke, K. Schulten, et al. (2009)
Science 326, 1412-1415
   Abstract »    Full Text »    PDF »
A ribosome-nascent chain sensor of membrane protein biogenesis in Bacillus subtilis.
S. Chiba, A. Lamsa, and K. Pogliano (2009)
EMBO J. 28, 3461-3475
   Abstract »    Full Text »    PDF »
Tryptophan Inhibits Proteus vulgaris TnaC Leader Peptide Elongation, Activating tna Operon Expression.
L. R. Cruz-Vera, R. Yang, and C. Yanofsky (2009)
J. Bacteriol. 191, 7001-7006
   Abstract »    Full Text »    PDF »
Large facilities and the evolving ribosome, the cellular machine for genetic-code translation.
A. Yonath (2009)
J R Soc Interface 6, S575-S585
   Abstract »    Full Text »    PDF »
23S rRNA Nucleotides in the Peptidyl Transferase Center Are Essential for Tryptophanase Operon Induction.
R. Yang, L. R. Cruz-Vera, and C. Yanofsky (2009)
J. Bacteriol. 191, 3445-3450
   Abstract »    Full Text »    PDF »
The Ribosome: a Metabolite-Responsive Transcription Regulator.
V. Stewart (2008)
J. Bacteriol. 190, 4787-4790
   Full Text »    PDF »
Conserved Residues Asp16 and Pro24 of TnaC-tRNAPro Participate in Tryptophan Induction of tna Operon Expression.
L. R. Cruz-Vera and C. Yanofsky (2008)
J. Bacteriol. 190, 4791-4797
   Abstract »    Full Text »    PDF »
Modulating the activity of the peptidyl transferase center of the ribosome.
M. Beringer (2008)
RNA 14, 795-801
   Abstract »    Full Text »    PDF »
Nascent Peptide-Mediated Translation Elongation Arrest of Arabidopsis thaliana CGS1 mRNA Occurs Autonomously.
H. Onouchi, Y. Haraguchi, M. Nakamoto, D. Kawasaki, Y. Nagami-Yamashita, K. Murota, A. Kezuka-Hosomi, Y. Chiba, and S. Naito (2008)
Plant Cell Physiol. 49, 549-556
   Abstract »    Full Text »    PDF »
RNA-based regulation of genes of tryptophan synthesis and degradation, in bacteria.
C. Yanofsky (2007)
RNA 13, 1141-1154
   Abstract »    Full Text »    PDF »
Ribosomal Features Essential for tna Operon Induction: Tryptophan Binding at the Peptidyl Transferase Center.
L. R. Cruz-Vera, A. New, C. Squires, and C. Yanofsky (2007)
J. Bacteriol. 189, 3140-3146
   Abstract »    Full Text »    PDF »
Ribosome Recycling Factor and Release Factor 3 Action Promotes TnaC-Peptidyl-tRNA Dropoff and Relieves Ribosome Stalling during Tryptophan Induction of tna Operon Expression in Escherichia coli.
M. Gong, L. R. Cruz-Vera, and C. Yanofsky (2007)
J. Bacteriol. 189, 3147-3155
   Abstract »    Full Text »    PDF »
Translational repression of mouse mu opioid receptor expression via leaky scanning.
K. Y. Song, C. K. Hwang, C. S. Kim, H. S. Choi, P.-Y. Law, L.-N. Wei, and H. H. Loh (2007)
Nucleic Acids Res. 35, 1501-1513
   Abstract »    Full Text »    PDF »
Translation of the poly(A) tail plays crucial roles in nonstop mRNA surveillance via translation repression and protein destabilization by proteasome in yeast.
S. Ito-Harashima, K. Kuroha, T. Tatematsu, and T. Inada (2007)
Genes & Dev. 21, 519-524
   Abstract »    Full Text »    PDF »
Downstream control of upstream open reading frames.
M. S. Sachs and A. P. Geballe (2006)
Genes & Dev. 20, 915-921
   Full Text »    PDF »
Changes produced by bound tryptophan in the ribosome peptidyl transferase center in response to TnaC, a nascent leader peptide.
L. R. Cruz-Vera, M. Gong, and C. Yanofsky (2006)
PNAS 103, 3598-3603
   Abstract »    Full Text »    PDF »
Overexpression of tnaC of Escherichia coli Inhibits Growth by Depleting tRNA2Pro Availability.
M. Gong, F. Gong, and C. Yanofsky (2006)
J. Bacteriol. 188, 1892-1898
   Abstract »    Full Text »    PDF »
Nascent peptide-mediated translation elongation arrest coupled with mRNA degradation in the CGS1 gene of Arabidopsis.
H. Onouchi, Y. Nagami, Y. Haraguchi, M. Nakamoto, Y. Nishimura, R. Sakurai, N. Nagao, D. Kawasaki, Y. Kadokura, and S. Naito (2005)
Genes & Dev. 19, 1799-1810
   Abstract »    Full Text »    PDF »
Translation of the first upstream ORF in the hepatitis B virus pregenomic RNA modulates translation at the core and polymerase initiation codons.
A. Chen, Y. F. Kao, and C. M. Brown (2005)
Nucleic Acids Res. 33, 1169-1181
   Abstract »    Full Text »    PDF »
pH Regulates Genes for Flagellar Motility, Catabolism, and Oxidative Stress in Escherichia coli K-12.
L. M. Maurer, E. Yohannes, S. S. Bondurant, M. Radmacher, and J. L. Slonczewski (2005)
J. Bacteriol. 187, 304-319
   Abstract »    Full Text »    PDF »
Ribosome Stalling during Translation Elongation Induces Cleavage of mRNA Being Translated in Escherichia coli.
T. Sunohara, K. Jojima, H. Tagami, T. Inada, and H. Aiba (2004)
J. Biol. Chem. 279, 15368-15375
   Abstract »    Full Text »    PDF »
A nascent polypeptide domain that can regulate translation elongation.
P. Fang, C. C. Spevak, C. Wu, and M. S. Sachs (2004)
PNAS 101, 4059-4064
   Abstract »    Full Text »    PDF »
Translational regulation of BACE-1 expression in neuronal and non-neuronal cells.
D. De Pietri Tonelli, M. Mihailovich, A. Di Cesare, F. Codazzi, F. Grohovaz, and D. Zacchetti (2004)
Nucleic Acids Res. 32, 1808-1817
   Abstract »    Full Text »    PDF »
Factors That Influence Selection of Coding Resumption Sites in Translational Bypassing: MINIMAL CONVENTIONAL PEPTIDYL-tRNA:mRNA PAIRING CAN SUFFICE.
A. J. Herr, N. M. Wills, C. C. Nelson, R. F. Gesteland, and J. F. Atkins (2004)
J. Biol. Chem. 279, 11081-11087
   Abstract »    Full Text »    PDF »
Nascent-peptide-mediated ribosome stalling at a stop codon induces mRNA cleavage resulting in nonstop mRNA that is recognized by tmRNA.
RNA 10, 378-386
   Abstract »    Full Text »    PDF »
A Transcriptional Pause Synchronizes Translation with Transcription in the Tryptophanase Operon Leader Region.
F. Gong and C. Yanofsky (2003)
J. Bacteriol. 185, 6472-6476
   Abstract »    Full Text »    PDF »
Ligand crowding at a nascent signal sequence.
G. Eisner, H.-G. Koch, K. Beck, J. Brunner, and M. Muller (2003)
J. Cell Biol. 163, 35-44
   Abstract »    Full Text »    PDF »
Identifying the methyltransferases for m5U747 and m5U1939 in 23S rRNA using MALDI mass spectrometry.
C. T. Madsen, J. Mengel-Jorgensen, F. Kirpekar, and S. Douthwaite (2003)
Nucleic Acids Res. 31, 4738-4746
   Abstract »    Full Text »    PDF »
Co-translational, Intraribosomal Cleavage of Polypeptides by the Foot-and-mouth Disease Virus 2A Peptide.
P. de Felipe, L. E. Hughes, M. D. Ryan, and J. D. Brown (2003)
J. Biol. Chem. 278, 11441-11448
   Abstract »    Full Text »    PDF »
Using Studies on Tryptophan Metabolism to Answer Basic Biological Questions.
C. Yanofsky (2003)
J. Biol. Chem. 278, 10859-10878
   Full Text »    PDF »
BIOCHEMISTRY: Sense and Sensitivity--Controlling the Ribosome.
M. S. Sachs and A. P. Geballe (2002)
Science 297, 1820-1821
   Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882