Crystallin-{alpha}B Regulates Skeletal Muscle Homeostasis via Modulation of Argonaute2 Activity [RNA]

April 29th, 2014 by Neppl, R. L., Kataoka, M., Wang, D.-Z.

The core functional machinery of the RNAi pathway is the RNA-induced silencing complex (RISC), wherein Argonaute2 (Ago2) is essential for siRNA directed endonuclease activity and RNAi/miRNA-mediated gene silencing. Crystallin-αB (CryAB) is a small heat shock protein involved in preventing protein aggregation. We demonstrate that CryAB interacts with the N- and C-termini of Ago2, not the catalytic site defined by the convergence of the PAZ, MID, and PIWI domains. We further demonstrate significantly reduced Ago2 activity in the absence of CryAB, highlighting a novel role of CryAB in the mammalian RNAi/miRNA pathway. In skeletal muscle of CryAB null mice we observe a shift in the hypertrophy-atrophy signaling axis towards atrophy under basal conditions. More over, loss-of CryAB altered the capability of satellite cell to regenerate skeletal muscle. These studies establish that CryAB is necessary for normal Ago2/RISC activity and cellular homeostasis in skeletal muscle.