Mitochondrial circular RNA MT-RNR2 declines with age and links to TCA cycle
Feb 23rd 2026
Analysis of human PBMCs and senescent fibroblasts shows circMT-RNR2 is depleted with age, requires the mitochondrial RNA-binding protein GRSF1, and associates with TCA cycle enzymes and metabolites.
- Total RNA sequencing of PBMCs from 11 young and 11 old donors found far fewer mitochondrial circular RNA junctions in the old group.
- The most abundant mitochondrial circular RNAs map to MT-RNR2 and are reduced in old PBMCs and in senescent WI-38 fibroblasts.
- PAR-CLIP shows mitochondrial RBP GRSF1 binds linear and circular MT-RNR2 and identifies a UGxxGGUU RNA motif at binding sites.
- RNP immunoprecipitation indicates MT-RNR2 co-precipitates with TCA cycle enzymes SUCLG1 and SDHA.
- GRSF1 knockdown lowers circMT-RNR2 and fumarate and succinate levels and speeds cellular senescence, while reintroducing circMT-RNR2 restores metabolite levels and partially rescues senescence markers.
- The authors propose circMT-RNR2 may scaffold metabolic enzymes to promote the TCA cycle, but the circularization mechanism in mitochondria and causal pathways require further validation.