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

Keiko Horiuchi, Michihisa Umetani, Takashi Minami, Hiroto Okayama, Shinji Takada, Masayuki Yamamoto, Hiroyuki Aburatani, Patrick C. Reid, David E. Housman, Takao Hamakubo, Tatsuhiko Kodama

Research output: Contribution to journalArticle

73 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)17278-17283
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number46
DOIs
StatePublished - Nov 14 2006

Keywords

  • Cell-cycle regulation
  • mRNA stability

ASJC Scopus subject areas

  • General

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