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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Neppl, Ronald L. Wang, Da-zhi Kataoka, Masaharu |
| Description | Author Affiliation: Neppl RL ( From the Department of Cardiology, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115 and rneppl@enders.tch.harvard.edu.); Kataoka M ( From the Department of Cardiology, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115 and.); Wang DZ ( From the Department of Cardiology, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115 and the Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138 dwang@enders.tch.harvard.edu.) |
| 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- B (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. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 24 |
| Volume Number | 289 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2014-06-13 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Argonaute Proteins Metabolism Homeostasis Muscle, Skeletal Alpha-Crystallin B Chain Animals Chemistry Genetics Binding Sites Catalytic Domain HEK293 Cells Mice MicroRNAs Growth & Development Physiology Protein Binding RNA-Induced Silencing Complex Regeneration Satellite Cells, Skeletal Muscle Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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