Long non-coding RNA-dependent mechanism to regulate heme biosynthesis and erythrocyte development.
Long non-coding RNA-dependent mechanism to regulate heme biosynthesis and erythrocyte development.
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长非编码RNA依赖机制调节血红素生物合成和红细胞发育
DOI：
10.1038/s41467-018-06883-x
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发表时间：
2018-10-22
影响因子：
16.6
通讯作者：
Shi L
中科院分区：
文献类型：
--
作者：
Liu J;Li Y;Tong J;Gao J;Guo Q;Zhang L;Wang B;Zhao H;Wang H;Jiang E;Kurita R;Nakamura Y;Tanabe O;Engel JD;Bresnick EH;Zhou J;Shi L
除了作为酶的辅助基团和血红蛋白结构成分外，血红素是红细胞发育和功能的重要稳态调节剂。虽然lncrna调节多种生理和病理细胞过程，但它们在血红素依赖机制中的参与在很大程度上尚未被探索。在这项研究中，我们阐明了lncRNA （UCA1）介导的调节人红细胞血红素代谢的机制。我们发现UCA1的表达在人红细胞成熟过程中受到动态调控，在原红细胞中表达最多。UCA1缺失主要损害血红素生物合成并在原红细胞阶段阻止红细胞分化。机制分析表明，UCA1与RNA结合蛋白PTBP1物理相互作用，UCA1作为RNA支架将PTBP1招募到alas2mrna，从而稳定alas2mrna。这些结果定义了lncrna介导的转录后机制，为基本血红素生物合成过程如何作为红细胞发育的决定因素进行调节提供了一个新的维度。
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 toALAS2mRNA, which stabilizesALAS2mRNA. 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.
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影响因子：
5.3
作者：
Kang, Yoon-A;Sanalkumar, Rajendran;Bresnick, Emery H.
通讯作者：
Bresnick, Emery H.
影响因子：
4.6
作者：
Bian Z;Jin L;Zhang J;Yin Y;Quan C;Hu Y;Feng Y;Liu H;Fei B;Mao Y;Zhou L;Qi X;Huang S;Hua D;Xing C;Huang Z
通讯作者：
Huang Z
影响因子：
64.5
作者：
Bhatt DM;Pandya-Jones A;Tong AJ;Barozzi I;Lissner MM;Natoli G;Black DL;Smale ST
通讯作者：
Smale ST
影响因子：
16
作者：
Fujiwara T;O'Geen H;Keles S;Blahnik K;Linnemann AK;Kang YA;Choi K;Farnham PJ;Bresnick EH
通讯作者：
Bresnick EH
影响因子：
21.3
作者：
Knoch, KP;Bergert, H;Solimena, M
通讯作者：
Solimena, M