Destabilization of nucleophosmin mRNA by the HuR/KSRP complex is required for muscle fibre formation

被引：58

作者：

Cammas, Anne ^{[1
,2
]}

Sanchez, Brenda Janice ^{[1
]}

Lian, Xian Jin ^{[1
]}

Dormoy-Raclet, Virginie ^{[1
]}

van der Giessen, Kate ^{[1
]}

Lopez de Silanes, Isabel ^{[3
]}

Ma, Jennifer ^{[1
]}

Wilusz, Carol ^{[4
]}

Richardson, John ^{[5
]}

Gorospe, Myriam ^{[6
]}

Millevoi, Stefania ^{[2
]}

Giovarelli, Matteo ^{[7
]}

Gherzi, Roberto ^{[7
]}

Di Marco, Sergio ^{[1
]}

Gallouzi, Imed-Eddine ^{[1
]}

机构：

[1] McGill Univ, Dept Biochem, Goodman Canc Ctr, Montreal, PQ H3G 1Y6, Canada

[2] Ctr Rech Cancerol Toulouse, INSERM, UMR 1037, F-31432 Toulouse, France

[3] Spanish Natl Canc Res Ctr CNIO Telomeres & Telome, Mol Oncol Program, Madrid 28029, Spain

[4] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA

[5] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada

[6] NIA, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA

[7] Ist Nazl Ric Cancro IST, Lab Gene Express Regulat, I-16132 Genoa, Italy

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

关键词：

AU-RICH ELEMENTS; BINDING-PROTEIN; GENE-EXPRESSION; HUR; DECAY; PHOSPHORYLATION; DIFFERENTIATION; IDENTIFICATION; STABILIZATION; CELLS;

D O I：

10.1038/ncomms5190

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：16

共 60 条

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