Regulation of Tfam mRNA stability in skeletal muscle fiber types

Abstract

Changes in mRNA stability may serve as a regulatory mechanism for mitochondrial biogenesis in skeletal muscle. We hypothesized that oxidative capacity would be closely associated with a greater mRNA stability of proteins vital to organelle biogenesis, prompting an enhanced mitochondrial content. Using an in vitro decay assay, the mRNA stability of mitochondrial transcription factor A (Tfam) was assessed, since it regulates the expression of mitochondrial DNA (mtDNA). The decay of Tfam mRNA was slowest in low oxidative fast‐twitch white (FTW) muscle. Decay rates were 1.5‐ and 2.3‐fold greater in fast‐twitch red (FTR) and slow‐twitch red (STR) fibers. Despite this, steady Tfam mRNA levels were not different between fiber types, suggesting increases in transcription in oxidative muscle which parallel mRNA decay. Degradation of mRNA in fiber types matched similar differences in the mRNA destabilizing protein AUF1, particularly the p42 isoform, with a 4.5‐fold difference in protein expression between STR and FTW muscle. A more dramatic difference in the expression of the mRNA stabilizing protein HuR existed between fiber types, which may serve to restrain uncontrolled mRNA decay in highly oxidative muscle. Thus, oxidative muscle types exhibit faster rates of Tfam mRNA turnover than low oxidative muscle, suggesting more precise control of Tfam expression, and thus mtDNA levels, in response to metabolic stress.