RNA splicing during terminal erythropoiesis.
RNA splicing during terminal erythropoiesis.
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DOI：
10.1097/moh.0000000000000329
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发表时间：
2017-05
影响因子：
3.2
通讯作者：
Conboy JG
中科院分区：
文献类型：
--
作者：
Conboy JG
红细胞祖细胞在终末红细胞生成过程中经历了基因表达和细胞重塑的广泛变化，因此必须准确有效地剪接数千个前mrna。不同的剪接选择是由RNA结合蛋白（rbp）和RNA中顺式调节结合基序之间的相互作用决定的。这篇综述将集中在最近的研究，定义全基因组范围的剪接在红母细胞和讨论什么是已知的调控。高度纯化的红母细胞群体的RNA-seq分析揭示了外显子和内含子选择性剪接的广泛程序。在正常的红细胞生成过程中，特定阶段的剪接转变改变了优化红细胞生成所需的蛋白质同工型的结构和丰度。剪接调节因子的突变或缺乏通过破坏剪接程序成为骨髓发育不良综合征（MDS）患者造血疾病的基础。红细胞祖细胞执行一个复杂的选择性剪接程序，在转录后调节基因表达，最终在红细胞末期以分化阶段特异性的方式调节蛋白质组的结构和功能。该程序有助于驱动分化，并确保合成产生机械稳定红细胞所需的适当蛋白质同种异构体。关键剪接调节蛋白的突变或缺乏会破坏剪接程序从而引起疾病。
Erythroid progenitors must accurately and efficiently splice thousands of pre-mRNAs as the cells undergo extensive changes in gene expression and cellular remodeling during terminal erythropoiesis. Alternative splicing choices are governed by interactions between RNA binding proteins (RBPs) and cis-regulatory binding motifs in the RNA. This review will focus on recent studies that define the genome-wide scope of splicing in erythroblasts and discuss what is known about its regulation. RNA-seq analysis of highly purified erythroblast populations has revealed an extensive program of alternative splicing of both exons and introns. During normal erythropoiesis, stage-specific splicing transitions alter the structure and abundance of protein isoforms required for optimized red cell production. Mutation or deficiency of splicing regulators underlies hematopoietic disease in myelopdysplasia syndrome (MDS) patients via disrupting the splicing program. Erythroid progenitors execute an elaborate alternative splicing program that modulates gene expression post-transcriptionally, ultimately regulating the structure and function of the proteome in a differentiation stage-specific manner during terminal erythropoiesis. This program helps drives differentiation and ensures synthesis of the proper protein isoforms required to produce mechanically stable red cells. Mutation or deficiency of key splicing regulatory proteins disrupts the splicing program to cause disease.