TY - JOUR T1 - miR-486 is essential for muscle function and suppresses a dystrophic transcriptome JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202101215 VL - 5 IS - 9 SP - e202101215 AU - Adrienne Samani AU - Rylie M Hightower AU - Andrea L Reid AU - Katherine G English AU - Michael A Lopez AU - J Scott Doyle AU - Michael J Conklin AU - David A Schneider AU - Marcas M Bamman AU - Jeffrey J Widrick AU - David K Crossman AU - Min Xie AU - David Jee AU - Eric C Lai AU - Matthew S Alexander Y1 - 2022/09/01 UR - https://www.life-science-alliance.org/content/5/9/e202101215.abstract N2 - miR-486 is a muscle-enriched microRNA, or “myomiR,” that has reduced expression correlated with Duchenne muscular dystrophy (DMD). To determine the function of miR-486 in normal and dystrophin-deficient muscles and elucidate miR-486 target transcripts in skeletal muscle, we characterized mir-486 knockout mice (mir-486 KO). mir-486 KO mice developed disrupted myofiber architecture, decreased myofiber size, decreased locomotor activity, increased cardiac fibrosis, and metabolic defects were exacerbated in mir-486 KO:mdx5cv (DKO) mice. To identify direct in vivo miR-486 muscle target transcripts, we integrated RNA sequencing and chimeric miRNA eCLIP sequencing to identify key transcripts and pathways that contribute towards mir-486 KO and dystrophic disease pathologies. These targets included known and novel muscle metabolic and dystrophic structural remodeling factors of muscle and skeletal muscle contractile transcript targets. Together, our studies identify miR-486 as essential for normal muscle function, a driver of pathological remodeling in dystrophin-deficient muscle, a useful biomarker for dystrophic disease progression, and highlight the use of multiple omic platforms to identify in vivo microRNA target transcripts. ER -