Upstream Open Reading Frames: Molecular Switches in (patho)physiology

Overview

Journal Bioessays

Publisher Wiley

Specialties Biology
Cell Biology
Molecular Biology

Date 2010 Aug 21

PMID 20726009

Citations 89

Authors

Klaus Wethmar

Jeske J Smink

Achim Leutz

Affiliations

Soon will be listed here.

Abstract

Conserved upstream open reading frames (uORFs) are found within many eukaryotic transcripts and are known to regulate protein translation. Evidence from genetic and bioinformatic studies implicates disturbed uORF-mediated translational control in the etiology of human diseases. A genetic mouse model has recently provided proof-of-principle support for the physiological relevance of uORF-mediated translational control in mammals. The targeted disruption of the uORF initiation codon within the transcription factor CCAAT/enhancer binding protein β (C/EBPβ) gene resulted in deregulated C/EBPβ protein isoform expression, associated with defective liver regeneration and impaired osteoclast differentiation. The high prevalence of uORFs in the human transcriptome suggests that intensified search for mutations within 5' RNA leader regions may reveal a multitude of alterations affecting uORFs, causing pathogenic deregulation of protein expression.

Citing Articles

Tiny but mighty: Diverse functions of uORFs that regulate gene expression.

Zhong Z, Li Y, Sun Q, Chen D Comput Struct Biotechnol J. 2024; 23:3771-3779.

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Genetic knock-in of EIF2AK3 variants reveals differences in PERK activity in mouse liver and pancreas under endoplasmic reticulum stress.

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DNL343 is an investigational CNS penetrant eukaryotic initiation factor 2B activator that prevents and reverses the effects of neurodegeneration caused by the integrated stress response.

Yulyaningsih E, Suh J, Fanok M, Chau R, Solanoy H, Takahashi R Elife. 2024; 12.

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Ribosome decision graphs for the representation of eukaryotic RNA translation complexity.

Tierney J, Swirski M, Tjeldnes H, Mudge J, Kufel J, Whiffin N Genome Res. 2024; 34(4):530-538.

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Ribosome Decision Graphs for the Representation of Eukaryotic RNA Translation Complexity.

Tierney J, Swirski M, Tjeldnes H, Mudge J, Kufel J, Whiffin N bioRxiv. 2023; .

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