Abstract：
:Maintenance of skeletal muscle mass requires a dynamic balance between protein synthesis and tightly controlled protein degradation by the calpain, autophagy-lysosome, and ubiquitin-proteasome systems (proteostasis). Several sensing and gene-regulatory mechanisms act together to maintain this balance in response to changing conditions. Here, we show that deletion of the highly conserved Rbfox1 and Rbfox2 alternative splicing regulators in adult mouse skeletal muscle causes rapid, severe loss of muscle mass. Rbfox deletion did not cause a reduction in global protein synthesis, but it led to altered splicing of hundreds of gene transcripts, including capn3, which produced an active form of calpain3 protease. Rbfox knockout also led to a reduction in autophagy flux, likely producing a compensatory increase in general protein degradation by the proteasome. Our results indicate that the Rbfox-splicing factors are essential for the maintenance of skeletal muscle mass and proteostasis.
journal_name
Cell Repjournal_title
Cell reportsauthors
Singh RK,Kolonin AM,Fiorotto ML,Cooper TAdoi
10.1016/j.celrep.2018.06.017subject
Has Abstractpub_date
2018-07-03 00:00:00pages
197-208issue
1issn
2211-1247pii
S2211-1247(18)30912-4journal_volume
24pub_type
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