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Long non-coding RNA-dependent mechanism to regulate heme biosynthesis and erythrocyte development

Jinhua Liu, Yapu Li, Jingyuan Tong, Jie Gao, Qing Guo, Lingling Zhang, Bingrui Wang, Hui Zhao, Hongtao Wang, Erlie Jiang, Ryo Kurita, Yukio Nakamura, Osamu Tanabe, James Douglas Engel, Emery H. Bresnick, Jiaxi Zhou () and Lihong Shi ()
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Jinhua Liu: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Yapu Li: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Jingyuan Tong: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Jie Gao: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Qing Guo: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Lingling Zhang: Tianjin University of Commerce
Bingrui Wang: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Hui Zhao: Tianjin University of Commerce
Hongtao Wang: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Erlie Jiang: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Ryo Kurita: Japanese Red Cross Society, Department of Research and Development, Central Blood Institute
Yukio Nakamura: RIKEN BioResource Research Center, Cell Engineering Division
Osamu Tanabe: Tohoku University
James Douglas Engel: University of Michigan Medical School
Emery H. Bresnick: University of Wisconsin School of Medicine and Public Health
Jiaxi Zhou: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Lihong Shi: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract In addition to serving as a prosthetic group for enzymes and a hemoglobin structural component, heme is a crucial homeostatic regulator of erythroid cell development and function. While lncRNAs modulate diverse physiological and pathological cellular processes, their involvement in heme-dependent mechanisms is largely unexplored. In this study, we elucidated a lncRNA (UCA1)-mediated mechanism that regulates heme metabolism in human erythroid cells. We discovered that UCA1 expression is dynamically regulated during human erythroid maturation, with a maximal expression in proerythroblasts. UCA1 depletion predominantly impairs heme biosynthesis and arrests erythroid differentiation at the proerythroblast stage. Mechanistic analysis revealed that UCA1 physically interacts with the RNA-binding protein PTBP1, and UCA1 functions as an RNA scaffold to recruit PTBP1 to ALAS2 mRNA, which stabilizes ALAS2 mRNA. These results define a lncRNA-mediated posttranscriptional mechanism that provides a new dimension into how the fundamental heme biosynthetic process is regulated as a determinant of erythrocyte development.

Date: 2018
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DOI: 10.1038/s41467-018-06883-x

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