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

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 Survival Dynamics, Tsukuba 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 be elucidated. Here, we report that juvenile cardiomyocyte-specific PRMT1-deficient mice develop severe dilated cardiomyopathy and exhibit aberrant cardiac alternative splicing. Furthermore, we iden- tified previously undefined cardiac alternative splicing isoforms of four genes (Asb2, Fbxo40, Nrap,and Eif4a2) in PRMT1-cK0 mice and revealed that el 4A2 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 Japan splicing regulation.