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PMID: 7708701 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Adherence to the first-AUG rule when a second AUG codon follows closely upon the first.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 7 ·1995-03-28 ·Pages 2662-6

Kozak M

Abstract

The rule that eukaryotic ribosomes initiate translation exclusively at the 5' proximal AUG codon is abrogated under rare conditions. One circumstance that has been suggested to allow dual initiation is close apposition of a second AUG codon. A possible mechanism might be that the scanning 40S ribosomal subunit flutters back and forth instead of stopping cleanly at the first AUG. This hypothesis seems to be ruled out by evidence presented herein that in certain mRNAs, the first of two close AUG codons is recognized uniquely. To achieve this, the 5' proximal AUG has to be provided with the full consensus sequence; even small departures allow a second nearby AUG codon to be reached by leaky scanning. This context-dependent leaky scanning unexpectedly fails when the second AUG codon is moved some distance from the first. A likely explanation, based on analyzing the accessibility of a far-downstream AUG codon under conditions of initiation versus elongation, is that 80S elongating ribosomes advancing from the 5' proximal start site can mask potential downstream start sites.

MeSH Terms
Adenine Animals Base Sequence Chloramphenicol O-Acetyltransferase/biosynthesis,genetics Codon, Initiator/genetics Consensus Sequence DNA Primers Guanine Models, Genetic Molecular Sequence Data Peptide Chain Initiation, Translational/genetics Plasmids Protein Biosynthesis RNA, Messenger/biosynthesis,chemistry,genetics Rabbits Restriction Mapping Reticulocytes/metabolism Ribosomes/metabolism Transcription, Genetic Uracil
Chemicals
Codon, Initiator DNA Primers RNA, Messenger Uracil Guanine Chloramphenicol O-Acetyltransferase Adenine
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Kozak M
Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Piscataway 08854, USA.
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.92.7.2662
Published
1995-03-28
Pages
2662-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC42278
Subset
IM
Grants
NIGMS NIH HHS · GM33915 · United States
Corrections
ErratumIn
PMID: 7624384
External Links
PubMed source DOI: 10.1073/pnas.92.7.2662 PMC Full Text View journal details
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