Translational regulation by uORFs and start codon selection stringency [Reviews]

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 the GCN4/ATF4 mRNAs.

Source: Genes and Development - July 18, 2023 Category: Genetics & Stem Cells Authors: Dever, T. E., Ivanov, I. P., Hinnebusch, A. G. Tags: Translation Reviews Source Type: research