Muscleblind-like 1 (Mbnl1) regulates pre-mRNA alternative splicing during terminal erythropoiesis
Muscleblind-like 1 (Mbnl1) regulates pre-mRNA alternative splicing during terminal erythropoiesis
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DOI：
10.1182/blood-2013-12-542209
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发表时间：
2014-07-24
期刊：
影响因子：
20.3
通讯作者：
Lodish, Harvey F.
中科院分区：
文献类型：
--
作者：
Cheng, Albert W.;Shi, Jiahai;Lodish, Harvey F.
在红系终末发育过程中，受调控的异构体基因表达的范围和作用尚不清楚。我们发现了在终末红细胞生成过程中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的序列丰富了由Muscleblind-like （MBNL）剪接因子家族结合的基序。在培养的小鼠胎肝红系祖细胞中，敲低Mbnl1导致红系分化强烈受阻，并破坏受发育调控的Ndel1 mRNA外显子跳变，Ndel1 mRNA与Mbnl1结合，对红系末端增殖至关重要。这些发现揭示了一个意想不到的选择性剪接程序的范围和Mbnl1在红系终末分化中的重要性。
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.