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PMID: 11161792 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S. Review

Do the 5'untranslated domains of human cDNAs challenge the rules for initiation of translation (or is it vice versa)?

Genomics ·Vol. 70 ·No. 3 ·2000-12-15 ·Pages 396-406

Kozak M

Abstract

The validity of the scanning mechanism for initiation of translation has been questioned based on a compilation of human cDNA sequences that showed a high frequency of upstream ATG codons. However, closer scrutiny of those cDNAs upholds the opposite view: the 5'UTRs on most cDNAs are compatible with standard rules for initiation of translation, and those rules can be used to flag anomalous cDNAs that, upon checking, turn out to have been misinterpreted. Some of the problematic 5'UTR sequences that persist, after obvious errors in the cDNA library have been corrected, might derive from transcripts that are not intended to be translated. Examples are given of genes that, for regulatory reasons, produce transcripts that are truncated, or retain an intron, or are otherwise configured in a way that precludes translation. The existence of a cDNA proves that a gene is transcribed, but only that; not every cDNA derives from a functional mRNA. Along with providing practical guidelines for interpreting cDNA sequences, the scanning model provides a theoretical framework for understanding the effects of certain mutations in the 5'UTR that alter the translatability of mRNAs, thereby contributing to cancer and other human diseases.

MeSH Terms
5' Untranslated Regions Animals DNA, Complementary Humans Molecular Sequence Data Protein Biosynthesis
Chemicals
5' Untranslated Regions DNA, Complementary
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Kozak M
Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 675 Hoes Lane, Piscataway, New Jersey 08854, USA. [email protected]
Article Info
Journal
Genomics
Abbr.
Genomics
ISSN
0888-7543
Published
2000-12-15
Pages
396-406
Language
English
Region
United States
NLM ID
8800135
Subset
IM
Grants
NIGMS NIH HHS · GM33915 · United States
Databases
GENBANK
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