October 9 - 12, 2012
Building 10 & Natcher Conference Center
- General Schedule of Events
- Opening Plenary Session
- Concurrent Symposia Sessions
- Poster Sessions
- National Graduate Student Research Conference
- FARE Award Ceremony
- Special Exhibits on Resources for Intramural Research
- TSA Research Festival Exhibit Show
- Clinical Center Tours
- Research Festival Committees
- Past Research Festivals
AUF1 promotes myogenesis by enhancing Myf5 and Mef2c expression
| Wednesday, November 06, 2013 — Poster Session I | |||
|---|---|---|---|
4:00 p.m. – 6:00 p.m. |
FAES Academic Center (Upper-Level Terrace) |
NIA |
MOLBIO-20 |
Authors
- A.C. Panda
- K. Abdelmohsen
- E. Mercken
- J.L. Martindale
- R. de Cabo
- M. Gorospe
Abstract
Objective: To study the role of RNA-binding protein AUF1 in muscle cell differentiation Background: Loss of AUF1 accelerates aging in mouse and promotes cellular senescence. Here, we have investigated AUF1 function in skeletal muscle differentiation, an age-impaired process. Results: In C2C12 myocytes, where AUF1 levels increase at the onset of myogenesis and remain elevated through myocyte differentiation into myotubes, we discovered that AUF1 silencing delayed myogenesis. The association of AUF1 with myogenic mRNAs, studied by using RIP (RNA immunoprecipitation) assays, revealed that AUF1 binds to Myf5 and Mef2c mRNAs. AUF1 knockdown reduced both Myf5 and Mef2c proteins and these effects were attributed to the reduced translation of these mRNAs. AUF1 silencing also led to a reduction in Mef2c mRNA, likely mediated by a lesser-understood role of AUF1 in gene transcription. In vivo studies show that Mef2c levels are reduced during muscle atrophy and are restored as the muscle regenerates, mirroring the pattern of AUF1 abundance. Importantly, overexpression of Myf5 and/or Mef2c rescued the effects of AUF1-silencing as an inhibitor of myogenesis. Conclusions: Our findings indicate that AUF1 regulates myogenesis by promoting the expression of Myf5 and Mef2c through a combination of transcriptional and translational mechanisms.
