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PMID: 23804758 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, U.S. Gov't, Non-P.H.S.

miR-195 competes with HuR to modulate stim1 mRNA stability and regulate cell migration.

Nucleic acids research ·Vol. 41 ·No. 16 ·2013-09-00 ·Pages 7905-19

Zhuang R, Rao JN, Zou T, Liu L, Xiao L, Cao S, Hansraj NZ, Gorospe M, Wang JY

Abstract

Stromal interaction molecule 1 (Stim1) functions as a sensor of Ca2+ within stores and plays an essential role in the activation of store-operated Ca2+ entry (SOCE). Although lowering Stim1 levels reduces store-operated Ca2+ entry and inhibits intestinal epithelial repair after wounding, the mechanisms that control Stim1 expression remain unknown. Here, we show that cellular Stim1 abundance is controlled posttranscriptionally via factors that associate with 3'-untranslated region (3'-UTR) of stim1 mRNA. MicroRNA-195 (miR-195) and the RNA-binding protein HuR competed for association with the stim1 3'-UTR and regulated stim1 mRNA decay in opposite directions. Interaction of miR-195 with the stim1 3'-UTR destabilized stim1 mRNA, whereas the stability of stim1 mRNA increased with HuR association. Interestingly, ectopic miR-195 overexpression enhanced stim1 mRNA association with argonaute-containing complexes and increased the colocalization of tagged stim1 RNA with processing bodies (P-bodies); the translocation of stim1 mRNA was abolished by HuR overexpression. Moreover, decreased levels of Stim1 by miR-195 overexpression inhibited cell migration over the denuded area after wounding but was rescued by increasing HuR levels. In sum, Stim1 expression is controlled by two factors competing for influence on stim1 mRNA stability: the mRNA-stabilizing protein HuR and the decay-promoting miR-195.

MeSH Terms
3' Untranslated Regions Animals Cell Line Cell Movement/genetics ELAV Proteins/metabolism Epithelial Cells/cytology,metabolism Membrane Glycoproteins/genetics,metabolism MicroRNAs/metabolism RNA Stability RNA, Messenger/metabolism Rats Stromal Interaction Molecule 1
Chemicals
3' Untranslated Regions ELAV Proteins MIRN195 microRNA, rat Membrane Glycoproteins MicroRNAs RNA, Messenger Stim1 protein, rat Stromal Interaction Molecule 1
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Zhuang Ran
Department of Surgery, Cell Biology Group, University of Maryland School of Medicine, MD 21201, USA, Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201, USA, Department of Pathology, University of Maryland School of Medicine, MD 21201, USA and Laboratory of Genetics, National Institute on Aging-IRP, NIH, Baltimore, MD 21224, USA.
Rao Jaladanki N
Zou Tongtong
Liu Lan
Xiao Lan
Cao Shan
Hansraj Natasha Z
Gorospe Myriam
Wang Jian-Ying
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkt565
Published
2013-09-00
Epub
2013-00-26
Pages
7905-19
Language
English
Region
England
NLM ID
0411011
PMCID
PMC3763549
Subset
IM
Grants
NIDDK NIH HHS · DK68491 · United States
NIDDK NIH HHS · R01 DK057819 · United States
NIDDK NIH HHS · DK57819 · United States
NIDDK NIH HHS · T32 DK067872 · United States
NIDDK NIH HHS · DK61972 · United States
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1093/nar/gkt565 PMC Full Text View journal details
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