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, Lihong Shi

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

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.

Original languageEnglish
Article number4386
JournalNature communications
Volume9
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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