Fiche du document
2018
- doi: 10.1172/JCI94956
- issn: 0021-9738
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1172/JCI94956
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/29408805
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1558-8238
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_1F54AD670B3B6
info:eu-repo/semantics/openAccess , Copying allowed only for non-profit organizations , https://serval.unil.ch/disclaimer
Sujets proches
Template RNA Informational RNA Protein transcript Messenger ribonucleic acid mRNA Protein transcriptsCiter ce document
V. Chennupati et al., « Ribonuclease inhibitor 1 regulates erythropoiesis by controlling GATA1 translation. », Serveur académique Lausannois, ID : 10.1172/JCI94956
Métriques
Partage / Export
Résumé
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.