RNase P generated tRFSer-GCT promotes fat storage in adipocytes via Adrb2 signaling
Linyuan Shen, Yuhang Lei, Xue Zhao, Xinyi Wang, Dujun Chen, Kai Wang, Yi Zhong, Tianci Liao, Yiting Yang, Lei Chen, Ye Zhao, Lili Niu, Xiaofeng Zhou, Mailin Gan, Li Zhu
TL;DR
A mitochondrial RNA fragment called tRFSer-GCT promotes fat storage in fat cells by regulating a key receptor involved in metabolism.
Contribution
Discovery of a novel mitochondrial tRNA-derived fragment that regulates adipogenesis via the Adrb2 signaling pathway.
Findings
tRFSer-GCT is enriched in brown adipose tissue and correlates with mitochondrial abundance and adipogenic differentiation.
tRFSer-GCT promotes lipid accumulation in fat cells and localizes to mitochondria.
tRFSer-GCT downregulates Adrenoceptor Beta 2 and rescues adipose tissue accumulation in Hsd17b10-deficient mice.
Abstract
tRNA-derived small RNAs (tsRNAs) are emerging regulators of metabolism, but their roles in adipose tissue are not well defined. Here, we profiled tsRNA expression in mouse brown adipose tissue (BAT), gonadal white adipose tissues, and inguinal white adipose tissue (iWAT), revealing depot-specific patterns and a notable enrichment of mitochondrial tRF-5c fragments, especially tRF-1:29-chrM.Ser-GCT (tRFSer-GCT), in BAT. tRFSer-GCT expression correlated with mitochondrial abundance and increased during adipogenic differentiation and metabolic activation, both in vivo and in vitro. Functionally, tRFSer-GCT promoted adipogenesis and lipid accumulation in 3T3-L1 cells and localized to mitochondria. Mechanistically, tRFSer-GCT is generated from mitochondrial tRNASer-GCT by the Ribonuclease P complex (Trmt10c, Hsd17b10, Prorp), with Hsd17b10 being essential for its biogenesis and for normal…
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Taxonomy
TopicsAdipose Tissue and Metabolism · Adipokines, Inflammation, and Metabolic Diseases · Endoplasmic Reticulum Stress and Disease