2025-07-10 カロリンスカ研究所(KI)
<関連情報>
- https://news.ki.se/newly-discovered-molecule-may-explain-reduced-muscle-mass-in-type-2-diabetes
- https://www.science.org/doi/10.1126/sciadv.ads4371
2型糖尿病患者の骨格筋におけるヒト特異的lncRNA TMEM9B-AS1のダウンレギュレーションはリボソーム生合成に影響する Down-regulation of human-specific lncRNA TMEM9B-AS1 in skeletal muscle of people with type 2 diabetes affects ribosomal biogenesis
Ilke Sen, Jonathon A. B. Smith, Elena Caria, Iurii Orlov, […] , and Anna Krook
Science Advances Published:9 Jul 2025
DOI:https://doi.org/10.1126/sciadv.ads4371
Abstract
Long noncoding RNAs (lncRNAs) are important regulators of skeletal muscle physiology, with altered expression noted in several human diseases including type 2 diabetes. We report that TMEM9B-AS1, a previously uncharacterized lncRNA, is down-regulated in skeletal muscle of men with type 2 diabetes and skeletal muscle from individuals with sarcopenia. Silencing of TMEM9B-AS1 in primary human myotubes attenuated protein synthesis, concomitant with reduced phosphorylation of ribosomal protein S6. Moreover, we show that TMEM9B-AS1 plays a pivotal role in regulation of ribosomal biogenesis by facilitating messenger RNA stabilization of the transcription factor MYC through direct physical interaction with the RNA binding protein, insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1). Disrupted ribosomal biogenesis resulting from TMEM9B-AS1 silencing leads to decreased expression of muscle contractile and structural proteins important for maintenance of skeletal muscle mass and function. Collectively, our data reveal a role of TMEM9B-AS1 in skeletal muscle loss associated with metabolic disorders.
