HnRNP K-mediated translational control links NMHC IIA to erythroid enucleation

Abstract

Post-transcriptional regulation is crucial for structural and functional alterations in erythropoiesis. Enucleation of erythroid progenitors precedes reticulocyte release into circulation. In enucleated cells, reticulocyte 15-lipoxygenase (r15-LOX) initiates mitochondria degradation. Regulation of r15-LOX mRNA translation by hnRNP K ascertains timely r15-LOX synthesis in terminal maturation. K562 cells induced for erythroid maturation recapitulate enucleation and mitochondria degradation. HnRNP K depletion from maturing K562 cells results in enhanced enucleation, which even occurs maturation-independent. We performed RIP-Chip analysis to identify hnRNP K-interacting RNAs comprehensively. Non-muscle myosin heavy chain (NMHC) IIA mRNA co-purified with hnRNP K from non-induced K562 cells, but not from mature cells. NMHC IIA protein increase in erythroid maturation at constant NMHC IIA mRNA level indicates post-transcriptional regulation. We demonstrate that binding of hnRNP K KH domain 3 to a specific sequence element in the NMHC IIA mRNA 3'UTR mediates translation regulation in vitro. Importantly, elevated NMHC IIA expression results in erythroid maturation-independent enucleation as shown for hnRNP K depletion. Our data provide evidence that hnRNP K mediated regulation of NMHC IIA mRNA translation contributes to the control of enucleation in erythropoiesis.