miR-1 sustains muscle physiology by controlling V-ATPase complex assembly

Paula Gutiérrez-Pérez, Emilio M. Santillán, Thomas Lendl, Jingkui Wang, Anna Schrempf, Thomas L. Steinacker, Mila Asparuhova, Marlene Brandstetter, David Haselbach, Luisa Cochella

Research output: Contribution to journalArticlepeer-review


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 Caenorhabditis elegans, 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 C. elegans to humans, and we experimentally validated this in Drosophila. 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.

Original languageEnglish (US)
Article numbereabh1434
JournalScience Advances
Issue number42
StatePublished - Oct 2021
Externally publishedYes

ASJC Scopus subject areas

  • General


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