Figure 4.

Growth-Regulated Genes Modulate Protein Synthesis and Anabolic Signaling in Human Muscle Cells

RNAi targeting of individual members of the muscle mass-related gene network.

(A) mRNA expression of BCAT2, FKBP1A, NID2, and MBNL1 relative to their own control (100%) following treatment with a pool of multiple siRNAs targeting each gene (BCAT2, FKBP1A, NID2, and MBNL1), with IGF-1 used to increase primary muscle cell protein synthesis. *p<0.05, **p<0.01, ***p<0.001.

(B) Calculation of relative arbitrary units (RAUs) for mTOR Ser2448 and eEF2 Thr56, using phosphospecific antibodies (IGF-1 treatment in primary muscle cell in the presence or absence of FKBP1A and MBNL1 RNAi). *p<0.05, **p<0.01, ***p<0.001.

(C) Correlation matrix of the in vivo changes in gene expression covarying with the change in FKBP1A. All of the genes were also correlated with exercise training-induced alterations in muscle lean mass (see Method Details). Transcription factor binding site enrichment analysis (−1,500 to +500 nt from the start codon using CiiiDER and controlled for bias in the muscle transcriptome) revealed that 3 transcription factors (KLF9, NFIA, and RBPJ) potentially coordinate this FKBP1A-angiogenesis related transcriptional “module” (i.e., they are not enriched in the larger lean-mass growth-related transcriptional signature).