miR-1 sustains muscle physiology by controlling V-ATPase complex assembly.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34652942.
- Also identified by DOI 10.1126/sciadv.abh1434 and PMC identifier 8519577.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Muscle function requires unique structural and metabolic adaptations that can render muscle cells selectively vulnerable, with mutations in some ubiquitously expressed genes causing myopathies but sparing other tissues. We uncovered a muscle cell vulnerability by studying miR-1, a deeply conserved, muscle-specific microRNA whose ablation causes various muscle defects. Using <i>Caenorhabditis elegans</i>, we found that miR-1 represses multiple subunits of the ubiquitous vacuolar adenosine triphosphatase (V-ATPase) complex, which is essential for internal compartment acidification and metabolic signaling. V-ATPase subunits are predicted miR-1 targets in animals ranging from <i>C. elegans</i> to humans, and we experimentally validated this in <i>Drosophila</i>. Unexpectedly, up-regulation of V-ATPase subunits upon miR-1 deletion causes reduced V-ATPase function due to defects in complex assembly. These results reveal V-ATPase assembly as a conserved muscle cell vulnerability and support a previously unknown role for microRNAs in the regulation of protein complexes.