Work

RNase P generated tRFSer-GCT promotes fat storage in adipocytes via Adrb2 signaling

Year: 2025

Type: article

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 tissues (BAT), gonadal white adipose tissues (gWAT), and inguinal white adipose tissues (iWAT), revealing depot-specific patterns and a notable enrichment of mitochondrial tRF-5c fragments, especially tRF Ser-GCT (tRF-1:29-chrM.Ser-GCT), in BAT. tRF Ser-GCT expression correlated with mitochondrial abundance and increased during adipogenic differentiation and metabolic activation, both in vivo and in vitro . Functionally, tRF Ser-GCT promoted adipogenesis and lipid accumulation in 3T3-L1 cells and localized to mitochondria. Mechanistically, tRF Ser-GCT is generated from mitochondrial tRNA Ser-GCT by the RNase P (Ribonuclease P) complex (Trmt10c, Hsd17b10, Prorp), with Hsd17b10 being essential for its biogenesis and for normal adipocyte lipid metabolism. tRF Ser-GCT directly targets and downregulates Adrb2 (Adrenoceptor Beta 2), a key metabolic regulator. In vivo , restoring tRF Ser-GCT in Hsd17b10-deficient mice partially rescued adipose tissue accumulation and adipogenic gene expression. Together, these findings identify tRF Ser-GCT as a mitochondrial tsRNA that promotes adipogenesis via the RNase P–Adrb2 axis, revealing a new layer of tsRNA-mediated regulation in adipose tissue biology.

Source: Journal of Biological Chemistry

DOI: 10.1016/j.jbc.2025.110820