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Ellefsen, S.

Publications and source records attributed to Ellefsen, S..

2 recordsLinked to original sources

Human-specific lncRNA TMEM9B-AS1 is downregulated in skeletal muscle of individuals with type 2 diabetes and regulates ribosomal biogenesis

Long non-coding RNAs (lncRNAs) are important regulators of skeletal muscle physiology, with altered expression noted in several human diseases including type 2 diabetes. Here we report TMEM9B-AS1, a previously uncharacterized lncRNA, is downregulated in skeletal muscle of men with type 2 diabetes. Silencing of TMEM9B-AS1 in primary human myotubes attenuated protein synthesis, concomitant with reduced phosphorylation of ribosomal protein S6, a downstream target of ERK and mTOR pathways. Moreover, we provide evidence that TMEM9B-AS1 plays a pivotal role in the regulation of ribosomal biogenesis by facilitating mRNA stabilization of the transcription factor MYC through a direct physical interaction with the RNA-binding protein IGF2BP1. Disrupted ribosomal biogenesis resulting from TMEM9B-AS1 silencing is linked reduced skeletal muscle mass in type 2 diabetes, elucidating molecular mechanisms contributing to skeletal muscle loss in metabolic disease.

cell biology↗

Benefits of higher resistance-training volume depends on ribosome biogenesis

Resistance-exercise volume is a determinant of training outcomes. However not all individuals respond in a dose-dependent fashion. In this study, 34 healthy individuals (males n = 16, age 23.6 (4.1) years; females n = 18, 22.0 (1.3) years) performed moderate- (3 sets per exercise, MOD) and low-volume (1 set, LOW) resistance training contralateral fashion for 12 weeks (2-3 sessions x week-1) enabling intra-individual comparisons of effects of training modalities. Muscle cross-sectional area (CSA) and muscle strength was assessed at weeks 0 and 12, along with biopsy sampling (m. Vastus lateralis). Muscle biopsies were also sampled before and one hour after the fifth session (Week 2). MOD resulted in larger increases in muscle CSA (5.2 (3.8)% versus 3.7 (3.7)%, P < 0.001) and strength (3.4-7.7% difference, all P < 0.05). In muscle, this coincided with greater reductions in type IIX fibres from week 0 to week 12 (MOD, -4.6 vs. LOW - 3.2%-point), greater post-exercise (Week 2) phosphorylation of mTOR (12%), S6-kinase 1 (19%) and ribosomal protein S6 (28%, Week 2), greater rested-state total RNA (8.8%, Week 2) and greater exercise-induced elevation of c-Myc mRNA expression (25%, Week 2; all P < 0.05). Fifteen participants displayed robust benefits of MOD on muscle hypertrophy. This was associated with greater accumulation of total RNA at Week 2 in MOD vs. LOW as every 1% difference increased the odds of MOD benefit by 5.4% (P = 0.010). In conclusion, MOD led to on average greater adaptations to resistance training and dose-dependent hypertrophy was associated with volume-dependent regulation of total RNA at week 2. This suggests that ribosomal biogenesis regulates the dose-response relationship between training volume and muscle hypertrophy.\n\nKey pointsO_LIFor individuals showing suboptimal adaptations to resistance training, manipulation of training volume is a potential measure to facilitate responses. This remains unexplored in previous research.\nC_LIO_LIHere, 34 untrained individuals performed contralateral resistance training with moderate and low volume for 12 weeks. Overall, moderate volume led to larger increases in muscle cross-sectional area, strength and type II fibre-type transitions.\nC_LIO_LIThese changes coincided with greater activation of signaling pathways controlling muscle growth and greater induction of ribosome synthesis.\nC_LIO_LIFifteen individuals displayed clear benefit of moderate-volume training on muscle hypertrophy. This coincided with greater total RNA accumulation in the early-phase of the training period, suggesting that ribosomal biogenesis regulates the dose-response relationship between training volume and muscle hypertrophy.\nC_LIO_LIThese results demonstrate that there is a dose-dependent relationship between training volume and muscle hypertrophy. On the individual level, benefits of higher training volume was associated with increased ribosomal biogenesis.\nC_LI

physiology↗