Priority Research Paper Volume 13, Issue 11 pp 14557—14570
GRSF1 deficiency in skeletal muscle reduces endurance in aged mice
- 1 Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
- 2 Department of Biochemistry, Chungnam National University, Daejeon, Korea
Received: April 26, 2021 Accepted: May 27, 2021 Published: June 2, 2021https://doi.org/10.18632/aging.203151
How to Cite
Copyright: © 2021 Driscoll et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
GRSF1 is a mitochondrial RNA-binding protein important for maintaining mitochondrial function. We found that GRSF1 is highly expressed in cultured skeletal myoblasts differentiating into myotubes. To understand the physiological function of GRSF1 in vivo, we generated mice in which GRSF1 was specifically ablated in skeletal muscle. The conditional knockout mice (Grsf1cKO) appeared normal until 7-9 months of age. Importantly, however, a reduction of muscle endurance compared to wild-type controls was observed in 16- to 18-month old Grsf1cKO mice. Transcriptomic analysis revealed more than 200 mRNAs differentially expressed in Grsf1cKO muscle at this age. Notably, mRNAs encoding proteins involved in mitochondrial function, inflammation, and ion transport, including Mgarp, Cxcl10, Nfkb2, and Sln mRNAs, were significantly elevated in aged Grsf1cKO muscle. Our findings suggest that GRSF1 deficiency exacerbates the functional decline of aged skeletal muscle, likely through multiple downstream effector proteins.