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bioRxiv · 10.1101/2024.07.05.602204

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

Sen, I.·Smith, J. A. B.·Caria, E.·Savikj, M.·Lian, K.·Ellefsen, S.·Zierath, J. R.·Krook, A.
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Abstract

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.

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Sen, I., Smith, J. A. B., Caria, E., Savikj, M., Lian, K., Ellefsen, S., Zierath, J. R., Krook, A.. 2024-07-06. Human-specific lncRNA TMEM9B-AS1 is downregulated in skeletal muscle of individuals with type 2 diabetes and regulates ribosomal biogenesis. https://doi.org/10.1101/2024.07.05.602204

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