Wilms' Tumor 1-associating Protein Regulates G2/M Transition Through Stabilization of Cyclin A2 MRNA

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 Nov 8

PMID 17088532

Citations 80

Authors

Keiko Horiuchi

Michihisa Umetani

Takashi Minami

Hiroto Okayama

Shinji Takada

Masayuki Yamamoto

Hiroyuki Aburatani

Patrick C Reid

David E Housman

Takao Hamakubo

Tatsuhiko Kodama

Affiliations

Soon will be listed here.

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.

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