The RNA-binding protein HuR promotes cell migration and cell invasion by stabilizing the beta-actin mRNA in a U-rich-element-dependent manner.
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.
Dormoy-Raclet
Virginie
V
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
I
Clair
Eveline
E
Kurban
Ghada
G
Mazroui
Rachid
R
Di Marco
Sergio
S
von Roretz
Christopher
C
Pause
Arnim
A
Gallouzi
Imed-Eddine
IE
D000199:Actins / Q000235:genetics* / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002448:Cell Adhesion; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D034622:RNA Interference; D020871:RNA Stability; D034443:RNA Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics*; D022502:Stress Fibers / Q000378:metabolism
D000199:Actins; D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D038621:Regulatory Sequences, Ribonucleic Acid