Nematode telomerase RNA hitchhikes on introns of germline–up-regulated genes
Telomerase is a ribonucleoprotein complex that elongates telomeric DNA, ensuring germline immortality. In this study, we identified the <i>Caenorhabditis elegans</i> telomerase RNA component 1 (<i>terc-1</i>), as the first known telomerase RNA expressed as an intronic long noncoding RNA (lncRNA), embedded in an intron of germline-up-regulated gene <i>nmy-2</i>. <i>terc-1</i> 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 <i>terc-1</i> led to progressive telomere shortening and sterility in successive generations. Artificially transplanting the <i>nmy-2</i> 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.
Authors
- Hiroki Shibuya (ORCID: https://orcid.org/0000-0002-3400-0741)
- Shunsuke Tagami (ORCID: https://orcid.org/0000-0002-1720-3627)
- Michiaki Hamada (ORCID: https://orcid.org/0000-0001-9466-1034)
- Takefumi Kondo (ORCID: https://orcid.org/0000-0001-8127-1141)
- Masahiro Onoguchi (ORCID: https://orcid.org/0000-0002-6356-6736)
- Osamu Nishimura (ORCID: https://orcid.org/0000-0003-1969-2580)
- Tatsuyuki Yoshii (ORCID: https://orcid.org/0000-0002-3465-4219)
- Eriko Kajikawa
- Hirohide Saito (ORCID: https://orcid.org/0000-0002-8570-5784)
- Morié Ishida (ORCID: https://orcid.org/0000-0001-6361-1421)
- Io Yamamoto (ORCID: https://orcid.org/0009-0004-9862-4627)
- Mitsutaka Kadota (ORCID: https://orcid.org/0000-0002-1674-6697)
- Fumiya Ito
- Shunsuke Sumi (ORCID: https://orcid.org/0000-0003-1007-9472)
- Yutaka Takeda (ORCID: https://orcid.org/0009-0001-2711-1822)
- Jingjing Zhang (ORCID: https://orcid.org/0000-0003-0372-4314)
Institutions
- Hiroshima University (JP)
- Shinshu University (JP)
- Waseda University (JP)
- Kyoto University (JP)
- Quantitative BioSciences (US)
- RIKEN Center for Biosystems Dynamics Research (JP)
- Hiroshima International University (JP)
- National Institute of Advanced Industrial Science and Technology (JP)
- Nippon Medical School (JP)
- University of Gothenburg (SE)
- The University of Osaka (JP)
Publication Details
- Journal
- Science
- Published
- 2025-10-23
- DOI
- https://doi.org/10.1126/science.ads7778
- Citations
- 1
- Primary Topic
- CRISPR and Genetic Engineering
- Type
- article
- Field-Weighted Citation Impact
- 0.81