Instruction of Translating Ribosome by Nascent Peptide

Gong, Feng; Yanofsky, Charles

doi:10.1126/science.1073997

Cited by 229 publications

(237 citation statements)

References 27 publications

Supporting

Mentioning

218

Contrasting

Unclassified

Order By: Relevance

“…Such nascent chain-exit tunnel interactions serve as a widespread and critical mechanism of gene regulation (1)(2)(3)(4)(5)(6). In this mode of regulation, translation is accompanied by ongoing negotiation between the tunnel and the nascent polypeptide, which is in turn affected by either the nascent chain's engagement in protein localization or concentration of an antibiotic or a metabolic compound.…”

Section: Discussionmentioning

confidence: 99%

“…These studies revealed that the ribosome cannot necessarily complete translation of messages for any given amino acid sequences without any delay. Remarkably, programmed elongation arrest can serve as a novel mechanism of cellular regulation, for instance to monitor protein localization, metabolite concentration, and reception of an antibiotic (1)(2)(3)(4)(5)(6). Although regulatory nascent peptides having divergent stall-inducing amino acid sequences have been identified from different living organisms, their species-specificity and exchangeability among different systems have not been explored.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Recruitment of a species-specific translational arrest module to monitor different cellular processes

Chiba

Kanamori

Ueda

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Nascent chain-mediated translation arrest serves as a mechanism of gene regulation. A class of regulatory nascent polypeptides undergoes elongation arrest in manners controlled by the dynamic behavior of the growing chain; Escherichia coli SecM monitors the Sec protein export pathway and Bacillus subtilis MifM monitors the YidC membrane protein integration/folding pathway. We show that MifM and SecM interact with the ribosome in a speciesspecific manner to stall only the ribosome from the homologous species. Despite this specificity, MifM is not exclusively designed to monitor membrane protein integration because it can be converted into a secretion monitor by replacing the N-terminal transmembrane sequence with a secretion signal sequence. These results show that a regulatory nascent chain is composed of two modular elements, one devoted to elongation arrest and another devoted to subcellular targeting, and they imply that physical pulling force generated by the latter triggers release of the arrest executed by the former. The combinatorial nature may assure common occurrence of nascent chain-mediated regulation.stalling sequence | SpoIIIJ | SecA | exit tunnel

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Recruitment of a species-specific translational arrest module to monitor different cellular processes

Chiba

Kanamori

Ueda

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…1), one must consider the possible involvement of an additional mechanism(s) mediated by HCV core protein, such as selective translational inhibition of particular proteins, impaired intracellular/nuclear transport or impaired folding/maturation of certain proteins immediately after their synthesis. As for the selective translational inhibition of particular proteins, it was recently reported that a nascent peptide sequence of a bacterial protein could influence translation continuation or termination within a translating ribosome (11).…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C Virus Core Protein Selectively Inhibits Synthesis and Accumulation of p21/Waf1 and Certain Nuclear Proteins

Oka

Nagano-Fujii

Yoshida

et al. 2003

Microbiology and Immunology

View full text Add to dashboard Cite

By using a vaccinia virus‐T7 expression system, possible effects of hepatitis C virus (HCV) core protein on synthesis and accumulation of host cellular proteins transiently expressed in cultured cells were analyzed. Immunoblot and immunofluorescence analyses revealed that synthesis and accumulation of certain nuclear proteins, such as p21/Waf1, p53, proliferating cell nuclear antigen and c‐Fos, were strongly inhibited by HCV core protein. On the other hand, synthesis and accumulation of cytoplasmic proteins, such as 2′‐5′‐oligoadenylate synthetase (2′‐5′‐OAS), RNase L and MEK1, were barely affected by HCV core protein. Northern blot analysis showed that the degrees of mRNA expression for those proteins did not differ between HCV core protein‐expressing cells and the control, suggesting that the inhibition occurred at the post‐transcription level. Pulse‐labeling analysis suggested that HCV core protein strongly inhibited synthesis of p21/Waf1 at the translation level. Once being accumulated in the nucleus, p21/Waf1 stability was not significantly affected by HCV core protein. Mutants of HCV core protein C‐terminally deleted by 18 or 41 amino acids (aa), which were localized almost exclusively in the nucleus, lost their ability to inhibit synthesis/accumulation of p21/Waf1 whereas another mutant C‐terminally deleted by 8 aa still maintained the same properties (subcellular localization and the inhibitory effect) as the full‐length HCV core protein of 191 aa. Taken together, our present results suggest that expression of HCV core protein in the cytoplasm selectively inhibits synthesis of p21/Waf1 and some other nuclear proteins at the translation level.

show abstract

“…15 This tunnel was shown to undergo alterations associated with antibiotics resistant mutations, 55 to posses discriminating properties 35,56,57 and to actively participate in regulating intracellular cotranslational processes. [58][59][60] Experiments with the secM (secretion monitor) protein, 35 and the leader peptide of E. coli tryptophanase (tnaC) operon 57 are of particular interest. The sequences of both proteins contain a similar motif, which causes elongation arrest under specific conditions, in conjunction with the existence of cellular systems to which they belong.…”

Section: Tunnel Discrimination Of Nascent Proteinsmentioning

confidence: 99%

Functional aspects of ribosomal architecture: symmetry, chirality and regulation

Zarivach

Bashan

Berisio

et al. 2004

J of Physical Organic Chem

View full text Add to dashboard Cite

High-resolution structures of both ribosomal subunits revealed that most stages of protein biosynthesis, including decoding of genetic information, are navigated and controlled by the elaborate ribosomal architecturaldesign. Remote interactions govern accurate substrate alignment within a flexible active-site pocket [peptidyl transferase center (PTC)], and spatial considerations, due mainly to a universal mobile nucleotide, U2585, ensure proper chirality by interfering with D-amino-acids incorporation. tRNA translocation involves two correlated motions: overall mRNA/tRNA (messenger and transfer RNA) shift, and a rotation of the tRNA single-stranded aminoacylated-3 0 end around the bond connecting it with the tRNA helical-regions. This bond coincides with an axis passing through a sizable symmetry-related region, identified around the PTC in all large-subunit crystal structures. Propelled by a bulged universal nucleotide, A2602, positioned at the two-fold symmetry axis, and guided by a ribosomal-RNA scaffold along an exact pattern, the rotatory motion results in stereochemistry optimal for peptide-bond formation and in geometry ensuring nascent proteins entrance into their exit tunnel. Hence, confirming that ribosomes contribute positional rather than chemical catalysis, and that peptide bond formation is concurrent with A-to P-site tRNA passage. Connecting between the PTC, the decoding center, the tRNA entrance and exit points, the symmetry-related region can transfer intra-ribosomal signals between remote functional locations, guaranteeing smooth processivity of amino acids polymerization. Ribosomal proteins are involved in accurate substrate placement (L16), discrimination and signal transmission (L22) and protein biosynthesis regulation (CTC). Residing on the exit tunnel walls near its entrance, and stretching to its opening, protein-L22 can mediate ribosome response to cellular regulatory signals, since it can swing across the tunnel, causing gating and elongation arrest. Each of the protein CTC domains has a defined task. The N-terminal domain stabilizes the intersubunit-bridge confining the A-site-tRNA entrance. The middle domain protects the bridge conformation at elevated temperatures. The C-terminal domain can undergo substantial conformational rearrangements upon substrate binding, indicating CTC participation in biosynthesiscontrol under stressful conditions.

show abstract

Instruction of Translating Ribosome by Nascent Peptide

Cited by 229 publications

References 27 publications

Recruitment of a species-specific translational arrest module to monitor different cellular processes

Recruitment of a species-specific translational arrest module to monitor different cellular processes

Hepatitis C Virus Core Protein Selectively Inhibits Synthesis and Accumulation of p21/Waf1 and Certain Nuclear Proteins

Functional aspects of ribosomal architecture: symmetry, chirality and regulation

Contact Info

Product

Resources

About