Translational regulation by uORFs and start codon selection stringency

Author:

Dever Thomas E.,Ivanov Ivaylo P.,Hinnebusch Alan G.

Abstract

In addition to the main, protein-coding, open reading frame (mORF), many eukaryotic mRNAs contain upstream ORFs (uORFs) initiated at AUG or near-cognate codons residing 5′ of the mORF start site. Whereas translation of uORFs generally represses translation of the mORFs, a subset of uORFs serves as a nexus for regulating translation of the mORF. In this review, we summarize the mechanisms by which uORFs can repress or stimulate mRNA translation, highlight uORF-mediated translational repression involving ribosome queuing, and critically evaluate recently described alternatives to the delayed reinitiation model for uORF-mediated regulation of theGCN4/ATF4mRNAs.

Funder

Intramural Research Program

National Institutes of Health

Publisher

Cold Spring Harbor Laboratory

Subject

Developmental Biology,Genetics

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