2025/10/23 by Yutaka Takeda, Masahiro Onoguchi, Fumiya Ito +13 · 2 voices · 1 citation
Biochemistry, Genetics and Molecular Biology · Medicine · #CRISPR and Genetic Engineering #Telomeres, Telomerase, and Senescence #Genetics, Aging, and Longevity in Model Organisms
paper · doi:10.1126/science.ads7778
Telomerase is a ribonucleoprotein complex that elongates telomeric DNA, ensuring germline immortality. In this study, we identified the Caenorhabditis elegans telomerase RNA component 1 ( terc-1 ), as the first known telomerase RNA expressed as an intronic long noncoding RNA (lncRNA), embedded in an intron of germline–up-regulated gene nmy-2 . terc-1 undergoes splicing, polyadenylation, and nuclear RNA exosome–dependent maturation, stabilized by H/ACA small nucleolar ribonucleoproteins, thus co-opting the H/ACA small nucleolar RNA (snoRNA) biogenesis machinery. Mutations in terc-1 led to progressive telomere shortening and sterility in successive generations. Artificially transplanting the nmy-2 intron into the introns of germline-expressed genes but not non–germline-expressed genes restored germline immortality, highlighting the importance of genomic context. Our findings suggest that nematode telomerase RNA is a snoRNA-like intronic lncRNA that exploits the introns of germline–up-regulated genes to ensure species survival.