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PMID: 23824540 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

STAU1 binding 3' UTR IRAlus complements nuclear retention to protect cells from PKR-mediated translational shutdown.

Genes & development ·Vol. 27 ·No. 13 ·2013-07-01 ·Pages 1495-510

Elbarbary RA, Li W, Tian B, Maquat LE

Abstract

For a number of human genes that encode transcripts containing inverted repeat Alu elements (IRAlus) within their 3' untranslated region (UTR), product mRNA is efficiently exported to the cytoplasm when the IRAlus, which mediate nuclear retention, are removed by alternative polyadenylation. Here we report a new mechanism that promotes gene expression by targeting mRNAs that maintain their 3' UTR IRAlus: Binding of the dsRNA-binding protein Staufen1 (STAU1) to 3' UTR IRAlus inhibits nuclear retention so as to augment the nuclear export of 3' UTR IRAlus-containing mRNAs (IRAlus mRNAs). Moreover, we found that 3' UTR IRAlus-bound STAU1 enhances 3' UTR IRAlus mRNA translation by precluding protein kinase R (PKR) binding, which obviates PKR activation, eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, and repression of global cell translation. Thus, STAU1 binding to 3' UTR IRAlus functions along with 3' UTR IRAlus-mediated nuclear retention to suppress the shutdown of cellular translation triggered by PKR binding to endogenous cytoplasmic dsRNAs. We also show that a changing STAU1/PKR ratio contributes to myogenesis via effects on the 3' UTR IRAlus of mRNA encoding the microRNA-binding protein LIN28.

Keywords
PKR STAU1 inverted repeat Alu elements myogenesis nuclear export p54nrb translation
MeSH Terms
3' Untranslated Regions Alu Elements/genetics Cell Nucleus/metabolism Cells, Cultured Cytoskeletal Proteins/genetics,metabolism Gene Expression Regulation HEK293 Cells Humans Protein Binding RNA Transport RNA, Messenger/metabolism RNA-Binding Proteins/genetics,metabolism
Chemicals
3' Untranslated Regions Cytoskeletal Proteins RNA, Messenger RNA-Binding Proteins STAU1 protein, human
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Elbarbary Reyad A
Department of Biochemistry and Biophysics, School of Medicine and Dentistry.
Li Wencheng
Tian Bin
Maquat Lynne E
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
1549-5477
DOI
10.1101/gad.220962.113
Published
2013-07-01
Pages
1495-510
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC3713430
Subset
IM
Grants
NIGMS NIH HHS · R01 GM074593 · United States
NIGMS NIH HHS · R01 GM084089 · United States
NIGMS NIH HHS · R37 GM074593 · United States
Corrections
CommentIn
PMID: 24335473
External Links
PubMed source DOI: 10.1101/gad.220962.113 PMC Full Text View journal details
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