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PMID: 22841487 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

LincRNA-p21 suppresses target mRNA translation.

Molecular cell ·Vol. 47 ·No. 4 ·2012-08-24 ·Pages 648-55

Yoon JH, Abdelmohsen K, Srikantan S, Yang X, Martindale JL, De S, Huarte M, Zhan M, Becker KG, Gorospe M

Abstract

Mammalian long intergenic noncoding RNAs (lincRNAs) are best known for modulating transcription. Here we report a posttranscriptional function for lincRNA-p21 as a modulator of translation. Association of the RNA-binding protein HuR with lincRNA-p21 favored the recruitment of let-7/Ago2 to lincRNA-p21, leading to lower lincRNA-p21 stability. Under reduced HuR levels, lincRNA-p21 accumulated in human cervical carcinoma HeLa cells, increasing its association with JUNB and CTNNB1 mRNAs and selectively lowering their translation. With elevated HuR, lincRNA-p21 levels declined, which in turn derepressed JunB and β-catenin translation and increased the levels of these proteins. We propose that HuR controls translation of a subset of target mRNAs by influencing lincRNA-p21 levels. Our findings uncover a role for lincRNA as a posttranscriptional inhibitor of translation.

MeSH Terms
Base Sequence Carboxypeptidases/genetics,metabolism ELAV Proteins/genetics,metabolism HeLa Cells Humans MicroRNAs/genetics Molecular Sequence Data Protein Biosynthesis Proteolysis RNA Processing, Post-Transcriptional RNA, Long Noncoding/genetics RNA, Messenger/genetics RNA-Binding Proteins/genetics,metabolism Transcription, Genetic Tumor Cells, Cultured beta Catenin/genetics,metabolism
Chemicals
CTNNB1 protein, human ELAV Proteins MicroRNAs RNA, Long Noncoding RNA, Messenger RNA-Binding Proteins beta Catenin mirnlet7 microRNA, human Carboxypeptidases SCPEP1 protein, human
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Yoon Je-Hyun
Laboratory of Molecular Biology and Immunology, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
Abdelmohsen Kotb
Srikantan Subramanya
Yang Xiaoling
Martindale Jennifer L
De Supriyo
Huarte Maite
Zhan Ming
Becker Kevin G
Gorospe Myriam
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-4164
Published
2012-08-24
Epub
2012-00-26
Pages
648-55
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC3509343
Subset
IM
Grants
NCI NIH HHS · K99 CA149169 · United States
NCI NIH HHS · R00 CA149169 · United States
Intramural NIH HHS · ZIA AG000511-14 · United States
NCI NIH HHS · U54CA149169 · United States
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