Role of Ribonuclease inhibitor (RNH1) in haematopoietic stem cell function

Ribonuclease Inhibitor (RNH1) is an ubiquitously expressed 50-kDa leucine-rich repeat (LRR) protein. As suggested by its name, RNH1 binds to and inhibits pancreatic type ribonucleases. Further, RNH1 contains numerous cysteine residues whose sulfhydryl groups might play key structural roles and protect from oxidative damage. Despite of all these observations, the function of RNH1 in vivo remains unexplored. We recently published that RNH1 is important for embryonic development and regulates erythropoiesis by specifically regulating GATA1 mRNA translation. To understand RNH1 role in adult haematopoiesis, we generated Rnh1 conditional knockout mice and deleted RNH1 in adult haematopoietic stem cells (HSCs). Rnh1- deficiency in HSCs leads to increased numbers of myeloid cells but decreased lymphoid and erythroid cells, resembling emergency myelopoiesis phenotype. To understand the mechanism, we isolated long-term haematopoietic stem cells (LT-HSCs), short-term haematopoietic stem cells (ST-HSCs), and granulocyte monocyte progenitors (GMPs) and performed transcriptome analysis. We used three separate wild type (WT) and Rnh1-KO biological samples for the analysis.