Crystallin-αB regulates skeletal muscle homeostasis via modulation of Argonaute2 activity

Ronald L. Neppl, Masaharu Kataoka, Da Zhi Wang

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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/microRNA-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/microRNA pathway. In skeletal muscle of CryAB null mice, we observe a shift in the hypertrophy-atrophy signaling axis toward atrophy under basal conditions. Moreover, loss of CryAB altered the capability of satellite cells to regenerate skeletal muscle. These studies establish that CryAB is necessary for normal Ago2/RISC activity and cellular homeostasis in skeletal muscle.

Original languageEnglish
Pages (from-to)17240-17248
Number of pages9
JournalJournal of Biological Chemistry
Volume289
Issue number24
DOIs
Publication statusPublished - 2014 Jun 13
Externally publishedYes

Fingerprint

Crystallins
Muscle
Skeletal Muscle
Homeostasis
Modulation
RNA-Induced Silencing Complex
RNA Interference
MicroRNAs
Atrophy
Small Heat-Shock Proteins
Endonucleases
Gene Silencing
Hypertrophy
Small Interfering RNA
Machinery
Catalytic Domain
Agglomeration
Genes
Satellites

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Crystallin-αB regulates skeletal muscle homeostasis via modulation of Argonaute2 activity. / Neppl, Ronald L.; Kataoka, Masaharu; Wang, Da Zhi.

In: Journal of Biological Chemistry, Vol. 289, No. 24, 13.06.2014, p. 17240-17248.

Research output: Contribution to journalArticle

Neppl, Ronald L. ; Kataoka, Masaharu ; Wang, Da Zhi. / Crystallin-αB regulates skeletal muscle homeostasis via modulation of Argonaute2 activity. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 24. pp. 17240-17248.
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