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Ribonuclease DIS-3 promotes longevity by generating tRNA halves that inhibit translation via binding ribosomal proteins

ABSTRACT: Transfer RNA (tRNA) halves (tRHs) are generated via the cleavage of tRNAs and affect various biological processes, but their roles in aging and longevity remain poorly understood. Here, we determined the function of tRHs in aging by demonstrating that DIS-3/DIS3/RRP44 ribonuclease cleaved tRNAs for generating tRNA halves that promoted longevity. By performing a targeted genetic screen and subsequent biochemical analysis, we found that DIS-3/DIS3 catalyzed the generation of representative tRHs. We showed that dis-3 was crucial for longevity conferred by dietary restriction by upregulating SKN-1/NRF in the nematode Caenorhabditis elegans. Overexpression of 5′-tRH-Gln, a DIS-3 target, increased lifespan by reducing translation via binding ribosomal proteins. We further showed that mammalian DIS3 contributed to the generation of several tRHs and the prevention of premature cellular senescence. Overall, our data indicate that DIS-3/DIS3 is an evolutionarily conserved tRH-generating ribonuclease that counteracts aging.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE292138 | GEO | 2026/04/06

REPOSITORIES: GEO

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