肌肉盲样蛋白1（Mbnl1）在终末红细胞生成过程中调节前体mRNA的可变剪接。
Muscleblind-like 1 (Mbnl1) regulates pre-mRNA alternative splicing during terminal erythropoiesis.
作者信息
Cheng Albert W, Shi Jiahai, Wong Piu, Luo Katherine L, Trepman Paula, Wang Eric T, Choi Heejo, Burge Christopher B, Lodish Harvey F
机构信息
Whitehead Institute for Biomedical Research, Cambridge, MA; Computational and Systems Biology Program, and.
Whitehead Institute for Biomedical Research, Cambridge, MA;
出版信息
Blood. 2014 Jul 24;124(4):598-610. doi: 10.1182/blood-2013-12-542209. Epub 2014 May 28.
Abstract
The scope and roles of regulated isoform gene expression during erythroid terminal development are poorly understood. We identified hundreds of differentiation-associated isoform changes during terminal erythropoiesis. Sequences surrounding cassette exons of skipped exon events are enriched for motifs bound by the Muscleblind-like (MBNL) family of splicing factors. Knockdown of Mbnl1 in cultured murine fetal liver erythroid progenitors resulted in a strong block in erythroid differentiation and disrupted the developmentally regulated exon skipping of Ndel1 mRNA, which is bound by MBNL1 and critical for erythroid terminal proliferation. These findings reveal an unanticipated scope of the alternative splicing program and the importance of Mbnl1 during erythroid terminal differentiation.
摘要
在红细胞终末发育过程中，受调控的异构体基因表达的范围和作用尚不清楚。我们在终末红细胞生成过程中鉴定出数百种与分化相关的异构体变化。跳过外显子事件的盒式外显子周围序列富含肌肉盲样（MBNL）剪接因子家族所结合的基序。在培养的小鼠胎儿肝脏红细胞祖细胞中敲低Mbnl1会导致红细胞分化强烈受阻，并破坏Ndel1 mRNA的发育调控外显子跳跃，Ndel1 mRNA由MBNL1结合且对红细胞终末增殖至关重要。这些发现揭示了可变剪接程序出乎意料的范围以及Mbnl1在红细胞终末分化过程中的重要性。
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