Gene Set: HORIUCHI_WTAP_TARGETS_DN

Standard name HORIUCHI_WTAP_TARGETS_DN
Systematic name M10279
Brief description Genes down-regulated in primary endothelial cells (HUVEC) after knockdown of WTAP [GeneID=9589] by RNAi.
Full description or 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.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17088532   Authors: Horiuchi K,Umetani M,Minami T,Okayama H,Takada S,Yamamoto M,Aburatani H,Reid PC,Housman DE,Hamakubo T,Kodama T
Exact source Table 3S
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Organism Homo sapiens
Contributed by Leona Saunders (MSigDB Team)
Source platform AFFY_HG_U133
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Version history 3.0: First introduced

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