@article{7dd062d8b8d84faa9b52ea5d80b17e30,
title = "RBPMS is an RNA-binding protein that mediates cardiomyocyte binucleation and cardiovascular development",
abstract = "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 the 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. The 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 the isoform switching of the heart-enriched LIM domain protein Pdlim5. The loss of Rbpms leads to an 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.",
keywords = "alternative splicing, cardiomyocyte binucleation, hypertrabeculation, noncompaction cardiomyopathy, patent ductus arteriosus, Pdlim5, Rbpms, RNA-binding protein",
author = "Peiheng Gan and Zhaoning Wang and Morales, {Maria Gabriela} and Yu Zhang and Rhonda Bassel-Duby and Ning Liu and Olson, {Eric N}",
note = "Funding Information: We thank Cristina Rodriguez-Caycedo for maintaining the iPSC facility and providing technical instruction. We thank Dr. Andres Ramirez-Martinez for advice on the Rbpms KO strategy, and John McAnally for performing microinjections for generating Rbpms KO mice. We thank Jose Cabrera for graphics. We thank Dr. Wei Tan for performing mouse echocardiography analysis, and the Molecular Histopathology Core managed by John Shelton for help with histology, Drs. Jian Xu and Yoon Jung Kim from the Next Generation Sequencing Core Facility at Children{\textquoteright}s Research Institute for performing the Illumina sequencing, and Stephen Johnson for help with high-performance computing. We thank Dr. Miao Cui and other members of the Olson laboratory for helpful discussions. We are grateful to Dr. Henry M. Sucov (Medical University of South Carolina) for advice on cardiac histology. This work was supported by grants from the NIH ( HL-130253 , AR-071980, and HD-087351 ), the Fondation Leducq Transatlantic Networks of Excellence in Cardiovascular Research , and the Robert A. Welch Foundation (grant 1-0025 to E.N.O.). P.G. was supported by a postdoctoral fellowship from the American Heart Association ( 825635 ). Z.W. was supported by a predoctoral fellowship from the American Heart Association and the Harry S. Moss Heart Trust ( 19PRE34380436 ). Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = apr,
day = "25",
doi = "10.1016/j.devcel.2022.03.017",
language = "English (US)",
volume = "57",
pages = "959--973.e7",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "8",
}