RBPMS is an RNA-binding protein that mediates cardiomyocyte binucleation and cardiovascular development

Peiheng Gan, Zhaoning Wang, Maria Gabriela Morales, Yu Zhang, Rhonda Bassel-Duby, Ning Liu, Eric N Olson

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)959-973.e7
JournalDevelopmental cell
Volume57
Issue number8
DOIs
StatePublished - Apr 25 2022

Keywords

  • alternative splicing
  • cardiomyocyte binucleation
  • hypertrabeculation
  • noncompaction cardiomyopathy
  • patent ductus arteriosus
  • Pdlim5
  • Rbpms
  • RNA-binding protein

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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