Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41467-018-06883-x
Keywords
-
Categories
Funding
- National Key Research and Development Program of China Stem Cell and Translational Research [2016YFA0102300, 2017YFA0103100, 2017YFA0103102]
- CAMS Initiative for Innovative Medicine [2016-I2M-3-002, 2016-I2M-1-018, 2017-I2M-1-015]
- National Natural Science Foundation of China [31471291, 81870089, 81700105]
- CAMS Medical Epigenetics Research Center [2018PT31033]
- Tianjin Natural Science Foundation [15JCYBJC54500]
- NIH [DK50107, HL117658]
Ask authors/readers for more resources
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 post-transcriptional mechanism that provides a new dimension into how the fundamental heme biosynthetic process is regulated as a determinant of erythrocyte development.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available