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PMID: 17548472 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The RNA-binding protein HuR promotes cell migration and cell invasion by stabilizing the beta-actin mRNA in a U-rich-element-dependent manner.

Molecular and cellular biology ·Vol. 27 ·No. 15 ·2007-08-00 ·Pages 5365-80

Dormoy-Raclet V, Ménard I, Clair E, Kurban G, Mazroui R, Di Marco S, von Roretz C, Pause A, Gallouzi IE

Abstract

A high expression level of the beta-actin protein is required for important biological mechanisms, such as maintaining cell shape, growth, and motility. Although the elevated cellular level of the beta-actin protein is directly linked to the long half-life of its mRNA, the molecular mechanisms responsible for this effect are unknown. Here we show that the RNA-binding protein HuR stabilizes the beta-actin mRNA by associating with a uridine-rich element within its 3' untranslated region. Using RNA interference to knock down the expression of HuR in HeLa cells, we demonstrate that HuR plays an important role in the stabilization but not in the nuclear/cytoplasmic distribution of the beta-actin mRNA. HuR depletion in HeLa cells alters key beta-actin-based cytoskeleton functions, such as cell adhesion, migration, and invasion, and these defects correlate with a loss of the actin stress fiber network. Together our data establish that the posttranscriptional event involving HuR-mediated beta-actin mRNA stabilization could be a part of the regulatory mechanisms responsible for maintaining cell integrity, which is a prerequisite for avoiding transformation and tumor formation.

MeSH Terms
Actins/genetics,metabolism Antigens, Surface/metabolism Base Sequence Binding Sites Cell Adhesion Cell Movement Cell Nucleus/metabolism Cell Proliferation ELAV Proteins ELAV-Like Protein 1 HeLa Cells Humans Molecular Sequence Data Protein Binding RNA Interference RNA Stability RNA Transport RNA, Messenger/genetics,metabolism RNA, Small Interfering/metabolism RNA-Binding Proteins/metabolism Regulatory Sequences, Ribonucleic Acid/genetics Stress Fibers/metabolism
Chemicals
Actins Antigens, Surface ELAV Proteins ELAV-Like Protein 1 ELAVL1 protein, human RNA, Messenger RNA, Small Interfering RNA-Binding Proteins Regulatory Sequences, Ribonucleic Acid
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Dormoy-Raclet Virginie
Department of Biochemistry, and McGill Cancer Center, McGill University, McIntyre Building, Room 904, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6.
Ménard Isabelle
Clair Eveline
Kurban Ghada
Mazroui Rachid
Di Marco Sergio
von Roretz Christopher
Pause Arnim
Gallouzi Imed-Eddine
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.00113-07
Published
2007-08-00
Epub
2007-00-04
Pages
5365-80
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1952093
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.00113-07 PMC Full Text View journal details
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