美国哈佛医学院Vijay G. Sankaran、Anindita Basak等研究人员合作发现,LIN28B介导的BCL11A翻译调控对人类血红蛋白转换的调节。相关论文2020年1月20日在线发表于国际学术期刊《自然—遗传学》。
Title: Control of human hemoglobin switching by LIN28B-mediated regulation of BCL11A translation
Author: Anindita Basak, Mathias Munschauer, Caleb A. Lareau, Kara E. Montbleau, Jacob C. Ulirsch, Christina R. Hartigan, Monica Schenone, John Lian, Yaomei Wang, Yumin Huang, Xianfang Wu, Lee Gehrke, Charles M. Rice, Xiuli An, Helen A. Christou, Narla Mohandas, Steven A. Carr, Jane-Jane Chen, Stuart H. Orkin, Eric S. Lander, Vijay G. Sankaran
Issue&Volume: 2020-01-20
Abstract: Increased production of fetal hemoglobin (HbF) can ameliorate the severity of sickle cell disease and β-thalassemia1. BCL11A represses the genes encoding HbF and regulates human hemoglobin switching through variation in its expression during development2,3,4,5,6,7. However, the mechanisms underlying the developmental expression of BCL11A remain mysterious. Here we show that BCL11A is regulated at the level of messenger RNA (mRNA) translation during human hematopoietic development. Despite decreased BCL11A protein synthesis earlier in development, BCL11A mRNA continues to be associated with ribosomes. Through unbiased genomic and proteomic analyses, we demonstrate that the RNA-binding protein LIN28B, which is developmentally expressed in a pattern reciprocal to that of BCL11A, directly interacts with ribosomes and BCL11A mRNA. Furthermore, we show that BCL11A mRNA translation is suppressed by LIN28B through direct interactions, independently of its role in regulating let-7 microRNAs, and that BCL11A is the major target of LIN28B-mediated HbF induction. Our results reveal a previously unappreciated mechanism underlying human hemoglobin switching that illuminates new therapeutic opportunities.
DOI: 10.1038/s41588-019-0568-7
Source: https://www.nature.com/articles/s41588-019-0568-7
Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex
本期文章:《自然—遗传学》:Online/在线发表