Regulation of rDNA transcription and ribosome biogenesis at the onset of skeletal muscle hypertrophy

Abstract

We investigated the regulation of ribosomal (r)DNA gene transcription and ribosome production at the onset of skeletal muscle hypertrophy. Mice were subjected to functional overload of the plantaris muscle by bilateral removal of the synergist muscles. Mechanical loading resulted in muscle hypertrophy with an increase in rRNA content. rDNA transcription as determined by 45S pre‐RNA abundance paralleled the increase in rRNA content. Increased transcription and protein expression of c‐Myc and its downstream POL I regulon (POL1RB, TIF‐1A, PAF53, TTF1 & TAF1C) was consistent with the increase in rRNA. Other factors involved in rDNA transcription (UBF) and chromatin remodeling (WSTF) were induced by mechanical loading in a similar fashion. Chromatin‐IP revealed that these factors, together with histone H3 lysine 9 acetylation abundance relative to H3 were also enriched at the rDNA promoter. Our results demonstrate that mechanical loading induces ribosome production via epigenetic and transcriptional mechanisms at the rDNA promoter.Supported by the Swedish Research Council (VR) and the Swedish Nat Ctr for Sports Res (CIF)