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

IF 45.8 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-10-23 DOI:10.1126/science.ads7778

Yutaka Takeda, Masahiro Onoguchi, Fumiya Ito, Io Yamamoto, Shunsuke Sumi, Tatsuyuki Yoshii, Morié Ishida, Eriko Kajikawa, Jingjing Zhang, Osamu Nishimura, Mitsutaka Kadota, Shunsuke Tagami, Takefumi Kondo, Hirohide Saito, Michiaki Hamada, Hiroki Shibuya

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Abstract

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.

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线虫端粒酶RNA搭便车在种系上调基因的内含子上

端粒酶是一种核糖核蛋白复合物，可以延长端粒DNA，确保种系的不朽。在这项研究中，我们确定了秀丽隐杆线虫端粒酶RNA组分1 (terc-1)，作为已知的第一个以内含子长链非编码RNA （lncRNA）表达的端粒酶RNA，嵌入在种系上调基因nmi -2的内含子中。terc-1经历剪接、聚腺苷化和核RNA外泌体依赖的成熟，由H/ACA小核仁核糖核蛋白稳定，从而选择H/ACA小核仁RNA （snoRNA）生物发生机制。terc-1的突变导致端粒逐渐缩短和后代不育。将nmy-2内含子人工移植到生殖系表达基因的内含子中，而不是非生殖系表达基因的内含子中，可以恢复生殖系的不朽性，这突出了基因组背景的重要性。我们的研究结果表明，线虫端粒酶RNA是一种类似于snorna的内含子lncRNA，它利用种系向上调节基因的内含子来确保物种生存。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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