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Translational regulation by uORFs and start codon selection stringency

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...

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Detalles Bibliográficos
Autores principales: Dever, Thomas E., Ivanov, Ivaylo P., Hinnebusch, Alan G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393191/
https://www.ncbi.nlm.nih.gov/pubmed/37433636
http://dx.doi.org/10.1101/gad.350752.123
Descripción
Sumario: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.