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

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.