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

研究成果: Article査読

82 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)17278-17283
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
103
46
DOI
出版ステータスPublished - 2006 11 14
外部発表はい

ASJC Scopus subject areas

  • 一般

フィンガープリント

「Wilms' tumor 1-associating protein regulates G<sub>2</sub>/M transition through stabilization of cyclin A2 mRNA」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル