PRMT1 Deficiency in Mouse Juvenile Heart Induces Dilated Cardiomyopathy and Reveals Cryptic Alternative Splicing Products

Kazuya Murata, Weizhe Lu, Misuzu Hashimoto, Natsumi Ono, Masafumi Muratani, Kana Nishikata, Jun Dal Kim, Shizufumi Ebihara, Junji Ishida, Akiyoshi Fukamizu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Protein arginine methyltransferase 1 (PRMT1) catalyzes the asymmetric dimethylation of arginine residues in proteins and methylation of various RNA-binding proteins and is associated with alternative splicing in vitro. Although PRMT1 has essential in vivo roles in embryonic development, CNS development, and skeletal muscle regeneration, the functional importance of PRMT1 in the heart remains to be elucidated. Here, we report that juvenile cardiomyocyte-specific PRMT1-deficient mice develop severe dilated cardiomyopathy and exhibit aberrant cardiac alternative splicing. Furthermore, we identified previously undefined cardiac alternative splicing isoforms of four genes (Asb2, Fbxo40, Nrap, and Eif4a2) in PRMT1-cKO mice and revealed that eIF4A2 protein isoforms translated from alternatively spliced mRNA were differentially ubiquitinated and degraded by the ubiquitin-proteasome system. These findings highlight the essential roles of PRMT1 in cardiac homeostasis and alternative splicing regulation.

Original languageEnglish
Pages (from-to)200-213
Number of pages14
JournaliScience
Volume8
DOIs
StatePublished - 2018/10/26

Keywords

  • Cell Biology
  • Developmental Biology
  • Genetics
  • Molecular Biology

ASJC Scopus subject areas

  • General

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