Proteome-wide systems genetics identifies UFMylation as a regulator of skeletal muscle function

Proteome-wide systems genetics identifies UFMylation as a regulator of skeletal muscle function

Blog Article

Improving muscle function has great potential to improve the quality of life.To identify novel regulators of skeletal muscle metabolism and function, we performed a proteomic analysis of gastrocnemius muscle from 73 genetically distinct inbred mouse strains, and integrated the data with previously acquired genomics and >300 molecular/phenotypic traits via quantitative trait loci mapping and correlation network analysis.These data identified thousands of associations between protein abundance and phenotypes and can be Pot Holders accessed online (https://muscle.coffeeprot.

com/) to identify regulators of muscle function.We used this resource to prioritize targets for a functional genomic screen in human bioengineered skeletal muscle.This identified several negative regulators of muscle function including UFC1, an E2 ligase for protein UFMylation.We show UFMylation sheath is up-regulated in a mouse model of amyotrophic lateral sclerosis, a disease that involves muscle atrophy.

Furthermore, in vivo knockdown of UFMylation increased contraction force, implicating its role as a negative regulator of skeletal muscle function.