HuR/KSRP复合物使核磷蛋白mRNA不稳定是肌纤维形成所必需的。
Destabilization of nucleophosmin mRNA by the HuR/KSRP complex is required for muscle fibre formation.
作者信息
Cammas Anne, Sanchez Brenda Janice, Lian Xian Jin, Dormoy-Raclet Virginie, van der Giessen Kate, López de Silanes Isabel, Ma Jennifer, Wilusz Carol, Richardson John, Gorospe Myriam, Millevoi Stefania, Giovarelli Matteo, Gherzi Roberto, Di Marco Sergio, Gallouzi Imed-Eddine
机构信息
1] Department of Biochemistry, Goodman Cancer Center, McGill University, McIntyre Building Room 915B, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6 [2] INSERM, UMR 1037, Centre de Recherche en Cancérologie de Toulouse, 31432 Toulouse, France.
Department of Biochemistry, Goodman Cancer Center, McGill University, McIntyre Building Room 915B, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6.
出版信息
Nat Commun. 2014 Jun 27;5:4190. doi: 10.1038/ncomms5190.
HuR promotes myogenesis by stabilizing the MyoD, myogenin and p21 mRNAs during the fusion of muscle cells to form myotubes. Here we show that HuR, via a novel mRNA destabilizing activity, promotes the early steps of myogenesis by reducing the expression of the cell cycle promoter nucleophosmin (NPM). Depletion of HuR stabilizes the NPM mRNA, increases NPM protein levels and inhibits myogenesis, while its overexpression elicits the opposite effects. NPM mRNA destabilization involves the association of HuR with the decay factor KSRP as well as the ribonuclease PARN and the exosome. The C terminus of HuR mediates the formation of the HuR-KSRP complex and is sufficient for maintaining a low level of the NPM mRNA as well as promoting the commitment of muscle cells to myogenesis. We therefore propose a model whereby the downregulation of the NPM mRNA, mediated by HuR, KSRP and its associated ribonucleases, is required for proper myogenesis.
HuR通过在肌肉细胞融合形成肌管的过程中稳定MyoD、肌细胞生成素和p21的mRNA来促进肌生成。在此我们表明，HuR通过一种新的mRNA去稳定化活性，通过降低细胞周期启动子核仁磷酸蛋白（NPM）的表达来促进肌生成的早期步骤。HuR的缺失会使NPM mRNA稳定，增加NPM蛋白水平并抑制肌生成，而其过表达则会产生相反的效果。NPM mRNA的去稳定化涉及HuR与降解因子KSRP以及核糖核酸酶PARN和外泌体的结合。HuR的C末端介导HuR-KSRP复合物的形成，并且足以维持低水平的NPM mRNA以及促进肌肉细胞向肌生成的定向分化。因此，我们提出了一个模型，即由HuR、KSRP及其相关核糖核酸酶介导的NPM mRNA的下调是正常肌生成所必需的。
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