1. Ribonuclease inhibitor 1 regulates erythropoiesis by controlling GATA1 translation
- Author
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Chennupati, Vijaykumar, Veiga, Diogo F.T., Maslowski, Kendle M., Andina, Nicola, Tardivel, Aubry, Yu, Eric Chi-Wang, Stilinovic, Martina, Simillion, Cedric, Duchosal, Michel A., Quadroni, Manfredo, Roberts, Irene, Sankaran, Vijay G., MacDonald, H. Robson, Fasel, Nicolas, Angelillo-Scherrer, Anne, Schneider, Pascal, Hoang, Trang, and Allam, Ramanjaneyulu
- Subjects
Physiological aspects ,Genetic aspects ,Research ,Embryonic development -- Physiological aspects -- Genetic aspects -- Research ,Ribosomal proteins -- Physiological aspects -- Genetic aspects -- Research ,Erythropoiesis -- Physiological aspects -- Genetic aspects -- Research ,Gene expression -- Physiological aspects -- Research - Abstract
Introduction Regulation of gene expression is important for normal development. Recent studies show that ribosomal proteins (RPs) regulate gene expression by selectively facilitating translation of specific mRNAs (1, 2). For [...], Ribosomal proteins (RP) regulate specific gene expression by selectively translating subsets of mRNAs. Indeed, in Diamond-Blackfan anemia and [5q.sup.-] 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.sup.+] 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.
- Published
- 2018
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