RBPMS is an RNA-binding protein that mediates cardiomyocyte binucleation and cardiovascular development.
RBPMS is an RNA-binding protein that mediates cardiomyocyte binucleation and cardiovascular development.
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DOI：
10.1016/j.devcel.2022.03.017
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发表时间：
2022-04-25
影响因子：
11.8
通讯作者：
Olson, Eric N.
中科院分区：
文献类型：
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作者：
Gan, Peiheng;Wang, Zhaoning;Morales, Maria Gabriela;Zhang, Yu;Bassel-Duby, Rhonda;Liu, Ning;Olson, Eric N.
致密化不全型心肌病是一种常见的先天性心脏病，与心室肌细胞小梁形成异常和泵功能受损有关。这种疾病的遗传基础和潜在机制仍然难以捉摸。我们发现，遗传缺失的RNA结合蛋白与多剪接（Rbpms），一个未知的RNA结合因子，导致围产期死亡的小鼠由于先天性心血管缺陷。Rbpms的丢失导致发育过程中心肌细胞双核化和细胞周期停滞的过早发生。具有RBPMS基因缺失的人iPSC衍生的心肌细胞对胞质分裂具有类似的阻断。测序分析表明，RBPMS在RNA剪接中起作用，并影响参与细胞骨架信号通路的RNA。我们发现RBPMS介导心脏富集LIM结构域蛋白Pdlim 5的同种型转换。Rbpms的丢失导致Pdlim 5-短亚型的异常积累，破坏心肌细胞胞质分裂。我们的研究结果将过早的心肌细胞双核化与致密化不全心肌病联系起来，并强调了Rbpms在这一过程中的作用。Gan等人证明了未表征的RNA剪接因子Rbpms在小鼠心脏发育中的作用。Rbpms调节胚胎心肌细胞的胞质分裂，而缺乏Rbpms会导致胞质分裂失败、过早的双核和致密化不全心肌病。
Noncompaction cardiomyopathy is a common congenital cardiac disorder associated with abnormal ventricular cardiomyocyte trabeculation and impaired pump function. The genetic basis and underlying mechanisms of this disorder remain elusive. We show that genetic deletion of RNA binding protein with multiple splicing (Rbpms), an uncharacterized RNA binding factor, causes perinatal lethality in mice due to congenital cardiovascular defects. Loss of Rbpms causes premature onset of cardiomyocyte binucleation and cell cycle arrest during development. Human iPSC-derived cardiomyocytes with RBPMS gene deletion have a similar blockade to cytokinesis. Sequencing analysis revealed that RBPMS plays a role in RNA splicing and influences RNAs involved in cytoskeletal signaling pathways. We found that RBPMS mediates isoform switching of the heart-enriched LIM domain protein Pdlim5. Loss of Rbpms leads to abnormal accumulation of Pdlim5-short isoforms, disrupting cardiomyocyte cytokinesis. Our findings connect premature cardiomyocyte binucleation to noncompaction cardiomyopathy and highlight the role of Rbpms in this process. Gan et al. demonstrate the roles of an uncharacterized RNA splicing factor Rbpms in mouse heart development. Rbpms regulates cytokinesis of embryonic cardiomyocytes, while absence of Rbpms causes cytokinesis failure, premature binucleation, and noncompaction cardiomyopathy.
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影响因子：
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作者：
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