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Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17278-83. Epub 2006 Nov 6.

Wilms' tumor 1-associating protein regulates G2/M transition through stabilization of cyclin A2 mRNA.

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  • 1Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Meguro, Tokyo 153-8904, Japan.

Abstract

Wilms' tumor 1-associating protein (WTAP) has been reported to be a ubiquitously expressed nuclear protein. Although a relation to splicing factors has been postulated, its actual physiological function still remains to be elucidated. To investigate the role of WTAP, we generated WTAP-knockout mice and performed small interfering RNA (siRNA)-mediated knockdown analyses in primary cultured cells. In DNA microarrays using human umbilical vein endothelial cells, WTAP-targeted siRNA treatment resulted in markedly reduced expression of cell-cycle-related genes. siRNA-mediated WTAP knockdown down-regulated the stability of cyclin A2 mRNA through a nine-nucleotide essential sequence in cyclin A2 mRNA 3' UTR. WTAP knockdown induced G2 accumulation, which is partially rescued by adenoviral overexpression of cyclin A2. Moreover, WTAP-null mice exhibited proliferative failure with death resulting at approximately embryonic day 6.5, an etiology almost identical to cyclin A2-null mice. Collectively, these findings establish WTAP as an essential factor for the stabilization of cyclin A2 mRNA, thereby regulating G2/M cell-cycle transition.

PMID:
17088532
[PubMed - indexed for MEDLINE]
PMCID:
PMC1634838
Free PMC Article
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