title: The RNA in reticulocytes is not just debris: it is necessary for the final stages of erythrocyte formation.
abstract: Reticulocytes contain both RNA and micro-organelles and represent the last stage of erythropoiesis before full maturation to red blood cells (RBCs). Even though there is continuing synthesis of hemoglobin and membrane-bound proteins in reticulocytes, the small amount of RNA that they contain has been regarded as non-functional residual material. Here we show that this residual RNA is both functional and essential for further reticulocyte maturation. Reticulocytes from which the remnant RNA had been removed by exposure to RNase did not survive or mature into RBCs in either humans or mice. Conversely, reticulocytes treated with an RNase Inhibitor were able to form normal biconcave cells. Similarly, poor survival was also seen in reticulocytes in which protein synthesis had been blocked. To identify the signaling pathways involved we isolated RNAs in reticulocytes versus those present in fully matured erythroblasts cultured from hematopoietic stem cells. RNAs found in erythroblasts were related to exocytosis, metabolism, and signal transduction all of which are critical for maturation through reticulocyte and into a fully mature, biconcave erythrocyte. Our results suggest that the mRNA in reticulocytes has to be translated into novel proteins that act to preserve mitochondria and maintain cell membrane integrity as reticulocytes mature. These results enhance our understanding of the final stage of erythropoiesis and may clarify why in vitro-generated reticulocytes for transfusion purposes survive poorly.
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Hanyang University, Seoul, Republic of Korea.
authors.forename: EunMi
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Hanyang University, Seoul, Republic of Korea.
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
authors.forename: Jung Hye
authors.initials: JH
authors.lastname: Hwang
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
authors.forename: Jeong Kyu
authors.initials: JK
authors.lastname: Hoh
authors.affiliation: Department of Genetics, College of Medicine, Hanyang University, Seoul, Republic of Korea.
authors.forename: Youl-Hee
authors.initials: YH
authors.lastname: Cho
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Hanyang University, Seoul, Republic of Korea. Electronic address: doceunjung@hanyang.ac.kr.
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Baek
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001692:Biological Transport; D002454:Cell Differentiation; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D004722:Endoribonucleases / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D004920:Erythropoiesis; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D014176:Protein Biosynthesis; D012313:RNA / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012156:Reticulocytes / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D015398:Signal Transduction
chemical_list: D012333:RNA, Messenger; D012313:RNA; D004722:Endoribonucleases
keywords: Erythropoiesis; Protein biosynthesis; Red blood cell; Reticulocyte; Ribonuclease; mRNA