title: Translational control mediated by hnRNP K 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, also known as ALOX15) initiates mitochondria degradation. Regulation of r15-LOX mRNA translation by hnRNP K determines 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 independently of maturation. We performed RIP-Chip analysis to identify hnRNP K-interacting RNAs comprehensively. Non-muscle myosin heavy chain (NMHC) IIA (also known as MYH9) 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 levels 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.
authors.affiliation: Department of Intensive Care and Intermediate Care, Experimental Research Unit, University Hospital, RWTH Aachen University, Pauwelsstrasse 30, Aachen 52074, Germany.
authors.forename: Isabel S
authors.initials: IS
authors.lastname: Naarmann-de Vries
authors.affiliation: Department of Intensive Care and Intermediate Care, Experimental Research Unit, University Hospital, RWTH Aachen University, Pauwelsstrasse 30, Aachen 52074, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Brendle
authors.affiliation: Genomics Core Facility, EMBL, Meyerhofstraße 1, Heidelberg 69117, Germany.
authors.forename: Tomi
authors.initials: T
authors.lastname: Bähr-Ivacevic
authors.affiliation: Genomics Core Facility, EMBL, Meyerhofstraße 1, Heidelberg 69117, Germany.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Benes
authors.affiliation: Department of Intensive Care and Intermediate Care, Experimental Research Unit, University Hospital, RWTH Aachen University, Pauwelsstrasse 30, Aachen 52074, Germany dostareck@ukaachen.de aostareck@ukaachen.de.
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Ostareck
authors.affiliation: Department of Intensive Care and Intermediate Care, Experimental Research Unit, University Hospital, RWTH Aachen University, Pauwelsstrasse 30, Aachen 52074, Germany dostareck@ukaachen.de aostareck@ukaachen.de.
authors.forename: Antje
authors.initials: A
authors.lastname: Ostareck-Lederer
mesh_terms: D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D004912:Erythrocytes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D004920:Erythropoiesis; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis; D000072417:Protein Domains; D012333:RNA, Messenger
chemical_list: D034641:Heterogeneous-Nuclear Ribonucleoprotein K; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D012333:RNA, Messenger; C515716:ALOX15 protein, human; D001093:Arachidonate 15-Lipoxygenase; D018995:Myosin Heavy Chains
keywords: Enucleation; Erythropoiesis; NMHC IIA mRNA; Post-transcriptional regulation; hnRNP K