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PMID: 25420103 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Local slowdown of translation by nonoptimal codons promotes nascent-chain recognition by SRP in vivo.

Nature structural & molecular biology ·Vol. 21 ·No. 12 ·2014-12-00 ·Pages 1100-5

Pechmann S, Chartron JW, Frydman J

Abstract

The genetic code allows most amino acids a choice of optimal and nonoptimal codons. We report that synonymous codon choice is tuned to promote interaction of nascent polypeptides with the signal recognition particle (SRP), which assists in protein translocation across membranes. Cotranslational recognition by the SRP in vivo is enhanced when mRNAs contain nonoptimal codon clusters 35-40 codons downstream of the SRP-binding site, the distance that spans the ribosomal polypeptide exit tunnel. A local translation slowdown upon ribosomal exit of SRP-binding elements in mRNAs containing these nonoptimal codon clusters is supported experimentally by ribosome profiling analyses in yeast. Modulation of local elongation rates through codon choice appears to kinetically enhance recognition by ribosome-associated factors. We propose that cotranslational regulation of nascent-chain fate may be a general constraint shaping codon usage in the genome.

MeSH Terms
Codon/metabolism Fungal Proteins/metabolism Fungi/metabolism Peptides/metabolism Protein Biosynthesis Protein Transport Ribosomes/metabolism Signal Recognition Particle/metabolism
Chemicals
Codon Fungal Proteins Peptides Signal Recognition Particle
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Pechmann Sebastian
Department of Biology, Stanford University, Stanford, California, USA.
Chartron Justin W
Department of Biology, Stanford University, Stanford, California, USA.
Frydman Judith
Department of Biology, Stanford University, Stanford, California, USA.
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.2919
Published
2014-12-00
Epub
2014-00-24
Pages
1100-5
Language
English
Region
United States
NLM ID
101186374
PMCID
PMC4488850
Subset
IM
Grants
NIGMS NIH HHS · GM56433 · United States
NIGMS NIH HHS · F32 GM108325 · United States
NIGMS NIH HHS · GM108325 · United States
NIGMS NIH HHS · R01 GM056433 · United States
NIAID NIH HHS · R01 AI040085 · United States
NIGMS NIH HHS · R37 GM056433 · United States
NIAID NIH HHS · P01 AI091575 · United States
Corrections
CommentIn
PMID: 25469841
CommentIn
PMID: 25491102
External Links
PubMed source DOI: 10.1038/nsmb.2919 PMC Full Text View journal details
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