RT Journal Article
SR Electronic
T1 miR-486 is essential for muscle function and suppresses a dystrophic transcriptome
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101215
DO 10.26508/lsa.202101215
VO 5
IS 9
A1 Adrienne Samani
A1 Rylie M Hightower
A1 Andrea L Reid
A1 Katherine G English
A1 Michael A Lopez
A1 J Scott Doyle
A1 Michael J Conklin
A1 David A Schneider
A1 Marcas M Bamman
A1 Jeffrey J Widrick
A1 David K Crossman
A1 Min Xie
A1 David Jee
A1 Eric C Lai
A1 Matthew S Alexander
YR 2022
UL https://www.life-science-alliance.org/content/5/9/e202101215.abstract
AB 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.