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

Anne Cammas; Brenda Janice Sanchez; Xian Jin Lian; Virginie Dormoy-Raclet; Kate Van Der Giessen; Isabel López De Silanes; Jennifer Ma; Carol Wilusz; John Richardson; Myriam Gorospe; Stefania Millevoi; Matteo Giovarelli; Roberto Gherzi; Sergio Di Marco; Imed Eddine Gallouzi

doi:10.1038/ncomms5190

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

Anne Cammas, Brenda Janice Sanchez, Xian Jin Lian, Virginie Dormoy-Raclet, Kate Van Der Giessen, Isabel López De Silanes, Jennifer Ma, Carol Wilusz, John Richardson, Myriam Gorospe, Stefania Millevoi, Matteo Giovarelli, Roberto Gherzi, Sergio Di Marco, Imed Eddine Gallouzi

A.O.U. San Martino - IST, Istituto Nazionale Ricerca sul Cancro (GENOVA)

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	4190
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms5190
Publication status	Published - Jun 27 2014

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Chemistry(all)
Physics and Astronomy(all)

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10.1038/ncomms5190

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Cammas, A., Sanchez, B. J., Lian, X. J., Dormoy-Raclet, V., Van Der Giessen, K., De Silanes, I. L., Ma, J., Wilusz, C., Richardson, J., Gorospe, M., Millevoi, S., Giovarelli, M., Gherzi, R., Di Marco, S., & Gallouzi, I. E. (2014). Destabilization of nucleophosmin mRNA by the HuR/KSRP complex is required for muscle fibre formation. Nature Communications, 5, [4190]. https://doi.org/10.1038/ncomms5190

Destabilization of nucleophosmin mRNA by the HuR/KSRP complex is required for muscle fibre formation. / Cammas, Anne; Sanchez, Brenda Janice; Lian, Xian Jin; Dormoy-Raclet, Virginie; Van Der Giessen, Kate; De Silanes, Isabel López; Ma, Jennifer; Wilusz, Carol; Richardson, John; Gorospe, Myriam; Millevoi, Stefania; Giovarelli, Matteo; Gherzi, Roberto; Di Marco, Sergio; Gallouzi, Imed Eddine.

In: Nature Communications, Vol. 5, 4190, 27.06.2014.

Research output: Contribution to journal › Article › peer-review

Cammas, A, Sanchez, BJ, Lian, XJ, Dormoy-Raclet, V, Van Der Giessen, K, De Silanes, IL, Ma, J, Wilusz, C, Richardson, J, Gorospe, M, Millevoi, S, Giovarelli, M, Gherzi, R, Di Marco, S & Gallouzi, IE 2014, 'Destabilization of nucleophosmin mRNA by the HuR/KSRP complex is required for muscle fibre formation', Nature Communications, vol. 5, 4190. https://doi.org/10.1038/ncomms5190

Cammas, Anne ; Sanchez, Brenda Janice ; Lian, Xian Jin ; Dormoy-Raclet, Virginie ; Van Der Giessen, Kate ; De Silanes, Isabel López ; Ma, Jennifer ; Wilusz, Carol ; Richardson, John ; Gorospe, Myriam ; Millevoi, Stefania ; Giovarelli, Matteo ; Gherzi, Roberto ; Di Marco, Sergio ; Gallouzi, Imed Eddine. / Destabilization of nucleophosmin mRNA by the HuR/KSRP complex is required for muscle fibre formation. In: Nature Communications. 2014 ; Vol. 5.

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

abstract = "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.",

author = "Anne Cammas and Sanchez, {Brenda Janice} and Lian, {Xian Jin} and Virginie Dormoy-Raclet and {Van Der Giessen}, Kate and {De Silanes}, {Isabel L{\'o}pez} and Jennifer Ma and Carol Wilusz and John Richardson and Myriam Gorospe and Stefania Millevoi and Matteo Giovarelli and Roberto Gherzi and {Di Marco}, Sergio and Gallouzi, {Imed Eddine}",

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AU - Cammas, Anne

AU - Sanchez, Brenda Janice

AU - Lian, Xian Jin

AU - Dormoy-Raclet, Virginie

AU - Van Der Giessen, Kate

AU - De Silanes, Isabel López

AU - Ma, Jennifer

AU - Wilusz, Carol

AU - Richardson, John

AU - Gorospe, Myriam

AU - Millevoi, Stefania

AU - Giovarelli, Matteo

AU - Gherzi, Roberto

AU - Di Marco, Sergio

AU - Gallouzi, Imed Eddine

PY - 2014/6/27

Y1 - 2014/6/27

N2 - 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.

AB - 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.

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

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