PRR14 mediates mechanotransduction and regulates myofiber identity via MEF2C in skeletal muscle.

Abstract

Skeletal muscle is a crucial tissue for physical activity and energy metabolism. Muscle atrophy, characterized by the loss of muscle mass and strength, contributes to adverse outcomes among individuals. This study elucidated the involvement of the nuclear lamina component PRR14 in transmitting mechanical signals and mediating the impact of exercise on skeletal muscle. The expression of PRR14 demonstrated a positive correlation with exercise, while a decline in adult skeletal muscle is evident in disuse muscle conditions. Genetically, multiple single nucleotide polymorphisms (SNPs) within PRR14's genomic locus were linked with muscle mass and function. Specific knockout (KO) of skeletal muscle Prr14 in mice lead to muscle atrophy, validating the genetic association. By employing biochemical analysis and high-throughput sequencing techniques, including transcriptome profile and epigenome investigations such as Cleavage Under Targets and Tagmentation sequencing (CUT&Tag-seq) and Transposase-Accessible Chromatin sequencing (ATAC-seq), we discovered that PRR14's deficiency altered chromatin structure, regulated MEF2C's activity, and disrupted myofiber identity maintenance, ultimately causing muscle atrophy. Our finding highlights the crucial role of PRR14 in mechanotransduction and epigenetic regulation, offering new therapeutic avenues for skeletal muscle pathologies related to these mechanisms.