Nematode telomerase RNA hitchhikes on introns of germline-up-regulated genes

• 成果类型: Article
• 署名作者: Takeda, Yutaka; Onoguchi, Masahiro; Ito, Fumiya; Yamamoto, Io; Sumi, Shunsuke; Yoshii, Tatsuyuki; Ishida, Morie; Kajikawa, Eriko; Zhang, Jingjing; Nishimura, Osamu; Kadota, Mitsutaka; Tagami, Shunsuke; Kondo, Takefumi; Saito, Hirohide; Hamada, Michiaki; Shibuya, Hiroki
• 署名单位: RIKEN; Waseda University; Waseda University; National Institute of Advanced Industrial Science & Technology (AIST); University of Tokyo; Kyoto University; University of Gothenburg; RIKEN; RIKEN; Shinshu University; Hiroshima University; Kyoto University; Nippon Medical School; University of Osaka
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.ads7778
• 发表日期: 2025-10-23
• 页码: eads7778
• 关键词: tert promoter mutations; caenorhabditis-elegans; embryonic polarity; catalytic subunit; fission yeast; PATHWAY; localization; snornas; seq; end

摘要

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.