Ribonuclease inhibitor 1 regulates erythropoiesis by controlling GATA1 translation

Vijaykumar Chennupati, Diogo Ft Veiga, Kendle M Maslowski, Nicola Andina, Aubry Tardivel, Eric Chi-Wang Yu, Martina Stilinovic, Cedric Simillion, Michel A Duchosal, Manfredo Quadroni, Irene Roberts, Vijay G Sankaran, H Robson MacDonald, Nicolas Fasel, Anne Angelillo-Scherrer, Pascal Schneider, Trang Hoang, Ramanjaneyulu Allam

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)
166 Downloads (Pure)


Ribosomal proteins (RP) regulate specific gene expression by selectively translating subsets of mRNAs. Indeed, in Diamond-Blackfan anaemia and 5q- syndrome, mutations in RP genes lead to a specific defect in erythroid gene translation and cause anaemia. Little is known about the molecular mechanisms of selective mRNA translation and involvement of ribosomal-associated factors in this process. Ribonuclease inhibitor (RNH1) is an 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 to 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 knock down 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.

Original languageEnglish
Pages (from-to)1597-1614
Number of pages18
JournalJournal of Clinical Investigation
Issue number4
Early online date6 Feb 2018
Publication statusPublished - 2 Apr 2018


Dive into the research topics of 'Ribonuclease inhibitor 1 regulates erythropoiesis by controlling GATA1 translation'. Together they form a unique fingerprint.

Cite this