| First Author | Molendijk J | Year | 2022 |
| Journal | Elife | Volume | 11 |
| PubMed ID | 36472367 | Mgi Jnum | J:348829 |
| Mgi Id | MGI:7644000 | Doi | 10.7554/eLife.82951 |
| Citation | Molendijk J, et al. (2022) Proteome-wide systems genetics identifies UFMylation as a regulator of skeletal muscle function. Elife 11 |
| abstractText | 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 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 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. |
