The role of alternative translation start sites in the generation of human protein diversity

According to the scanning model, 40S ribosomal subunits initiate translation at the first (5' proximal) AUG codon they encounter. However, if the first AUG is in a suboptimal context, it may not be recognized, and translation can then initiate at downstream AUG(s). In this way, a single RNA can...

Full description

Saved in:
Bibliographic Details
Published in:Molecular genetics and genomics : MGG 2005-07, Vol.273 (6), p.491-496
Main Authors: Kochetov, Alex V, Sarai, Akinori, Rogozin, Igor B, Shumny, Vladimir K, Kolchanov, Nikolay A
Format: Article
Language:English
Subjects:
5' Untranslated Regions - genetics
Codon, Initiator - genetics
Humans
Intracellular Space - chemistry
Peptide Chain Initiation, Translational - genetics
Polymorphism, Genetic
Proteins
Proteins - analysis
Proteins - genetics
Proteins - metabolism
Ribonucleic acid
RNA
RNA, Messenger - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:According to the scanning model, 40S ribosomal subunits initiate translation at the first (5' proximal) AUG codon they encounter. However, if the first AUG is in a suboptimal context, it may not be recognized, and translation can then initiate at downstream AUG(s). In this way, a single RNA can produce several variant products. Earlier experiments suggested that some of these additional protein variants might be functionally important. We have analysed human mRNAs that have AUG triplets in 5' untranslated regions and mRNAs in which the annotated translational start codon is located in a suboptimal context. It was found that 3% of human mRNAs have the potential to encode N-terminally extended variants of the annotated proteins and 12% could code for N-truncated variants. The predicted subcellular localizations of these protein variants were compared: 31% of the N-extended proteins and 30% of the N-truncated proteins were predicted to localize to subcellular compartments that differed from those targeted by the annotated protein forms. These results suggest that additional AUGs may frequently be exploited for the synthesis of proteins that possess novel functional properties.
ISSN:1617-4615
1617-4623
DOI:10.1007/s00438-005-1152-7