Ribonuclease DIS3 delays aging and senescence by generating tRNA halves.

Seokjun G Ha, Hanseul Lee, Jisoo Park, Donghun Lee, Gee-Yoon Lee, Seokjin Ham, Sujeong Kwon, Sangsoon Park, Sieun S Kim, Yoonji Jung, Jongsun Lee, Jooyeon Sohn, Seon Woo A An, Heehwa G Son, Wooseon Hwang, Hyeong-In Kim, Eunseok Kang, Yoon Ki Kim, Gwangrog Lee, Seung-Jae V Lee

Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea. · pubmed

Paper

Abstract

Transfer RNA (tRNA) halves (tRHs) are generated via the cleavage of tRNAs, but their roles in aging and longevity remain poorly understood. Here, we demonstrate a direct role of tRHs in aging in metazoans. Through a genetic screen using Caenorhabditis elegans, we identify DIS-3/DIS3 as a ribonuclease that catalyzes tRH generation, including 5'-tRH-Gln and 5'-tRH-Asp, from tRNAs. Among them, 5'-tRH-Gln is essential for longevity conferred by various interventions, including dietary restriction. Generation of 5'-tRH-Gln reduces translation via ribosomal protein binding and upregulates the SKN-1/NRF transcription factor responsible for lifespan extension. We further show that mammalian DIS3 contributes to tRH generation and delays cellular senescence through translation downregulation by another tRH, 5'-tRH-Cys. Overall, our data demonstrate that DIS-3/DIS3 is an evolutionarily conserved tRH-generating ribonuclease that counteracts organismal and cellular aging.

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Research summary

The paper claims that DIS-3/DIS3 generates tRNA halves that play a crucial role in delaying aging and cellular senescence. This research addresses mechanisms that could potentially counteract aging, making it relevant to longevity studies.

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