Ribonuclease inhibitor 1 regulates erythropoiesis by controlling GATA1 translation.

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Serval ID
serval:BIB_1F54AD670B3B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Ribonuclease inhibitor 1 regulates erythropoiesis by controlling GATA1 translation.
Journal
The Journal of Clinical Investigation
Author(s)
Chennupati V., Veiga D.F., Maslowski K.M., Andina N., Tardivel A., Yu E.C., Stilinovic M., Simillion C., Duchosal M.A., Quadroni M., Roberts I., Sankaran V.G., MacDonald H.R., Fasel N., Angelillo-Scherrer A., Schneider P., Hoang T., Allam R.
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Publication state
Published
Issued date
2018
Peer-reviewed
Oui
Volume
128
Number
4
Pages
1597-1614
Language
english
Abstract
Ribosomal proteins (RP) regulate specific gene expression by selectively translating subsets of mRNAs. Indeed, in Diamond-Blackfan anemia and 5q- syndrome, mutations in RP genes lead to a specific defect in erythroid gene translation and cause anemia. Little is known about the molecular mechanisms of selective mRNA translation and involvement of ribosomal-associated factors in this process. Ribonuclease inhibitor 1 (RNH1) is a ubiquitously expressed protein that binds to and inhibits pancreatic-type ribonucleases. Here, we report that RNH1 binds to ribosomes and regulates erythropoiesis by controlling translation of the erythroid transcription factor GATA1. Rnh1-deficient mice die between embryonic days E8.5 and E10 due to impaired production of mature erythroid cells from progenitor cells. In Rnh1-deficient embryos, mRNA levels of Gata1 are normal, but GATA1 protein levels are decreased. At the molecular level, we found that RNH1 binds to the 40S subunit of ribosomes and facilitates polysome formation on Gata1 mRNA to confer transcript-specific translation. Further, RNH1 knockdown in human CD34+ progenitor cells decreased erythroid differentiation without affecting myelopoiesis. Our results reveal an unsuspected role for RNH1 in the control of GATA1 mRNA translation and erythropoiesis.
Keywords
Development, Embryonic development, Embryonic stem cells, Hematology
Pubmed
Web of science
Open Access
Yes
Create date
26/02/2018 9:34
Last modification date
06/02/2020 7:19
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