Chou Yu-Shu, Logeswaran Dhenugen, Chow Chi-Nga, L Dunn Phoebe, Podlevsky Joshua D, Liu Tianxiang, Akhter Khadiza, Chen Julian J-L
School of Molecular Sciences, Arizona State University, Tempe, AZ 85281.
School of Life Sciences, Arizona State University, Tempe, AZ 85281.
Proc Natl Acad Sci U S A. 2025 Mar 4;122(9):e2424443122. doi: 10.1073/pnas.2424443122. Epub 2025 Feb 28.
Telomerase elongates telomeres to maintain chromosome stability in most eukaryotes. Despite extensive studies across eukaryotic kingdoms, the telomerase holoenzyme in arthropods remains poorly understood. In this study, we purify the telomerase ribonucleoprotein complex from the lepidopteran insect (fall armyworm) and identify a copurified 135-nucleotide telomerase RNA (TR) component. This miniature TR (sfTR), the smallest TR known to date, retains a universal pseudoknot structure and a structurally defined template. Despite its small size, sfTR assembles with the recombinant telomerase reverse transcriptase (sfTERT) protein in vivo to reconstitute telomerase activity for the synthesis of insect telomeric DNA repeats (TTAGG)n. The sfTR gene, like other animal TR genes, features an snRNA-type RNA polymerase II promoter. Uniquely, the sfTR transcript harbors a 5'-7-methylguanosine (MG) cap, as opposed to the more typical snRNA-type 2,2,7-trimethylguanosine (TMG) cap. The difference in 5'-cap is likely because sfTR lacks the H/ACA snoRNA biogenesis domain necessary for cap hypermethylation. Moreover, sfTR also lacks the CR4/5 regulatory domain that is indispensable in vertebrate TRs for telomerase activity. This degenerate sfTR complements an enigmatic sfTERT that is missing certain telomerase-specific elements yet catalytically active in the absence of sfTR. Thus, insects have evolved a simplified telomerase, consisting of a small noncoding RNA that retains only minimal attributes essential for telomerase function. The simplified insect telomerase demonstrates a plausible evolutionary pathway for the emergence of telomerase ribonucleoprotein complex, arising from an ancient reverse transcriptase associated with a simple templating RNA component in early eukaryotes.
在大多数真核生物中，端粒酶可延长端粒以维持染色体稳定性。尽管对真核生物界进行了广泛研究，但节肢动物中的端粒酶全酶仍知之甚少。在本研究中，我们从鳞翅目昆虫（草地贪夜蛾）中纯化了端粒酶核糖核蛋白复合物，并鉴定出一种共纯化的135个核苷酸的端粒酶RNA（TR）成分。这种微型TR（sfTR）是迄今为止已知最小的TR，保留了通用的假结结构和结构明确的模板。尽管其尺寸小，但sfTR在体内与重组端粒酶逆转录酶（sfTERT）蛋白组装，以重建用于合成昆虫端粒DNA重复序列（TTAGG）n的端粒酶活性。sfTR基因与其他动物TR基因一样，具有snRNA型RNA聚合酶II启动子。独特的是，sfTR转录本带有5'-7-甲基鸟苷（MG）帽，而不是更典型的snRNA型2,2,7-三甲基鸟苷（TMG）帽。5'-帽的差异可能是因为sfTR缺乏帽超甲基化所需的H/ACA snoRNA生物发生结构域。此外，sfTR还缺乏脊椎动物TR中端粒酶活性所必需的CR4/5调节结构域。这种退化的sfTR补充了一种神秘的sfTERT，该sfTERT缺少某些端粒酶特异性元件，但在没有sfTR的情况下具有催化活性。因此，昆虫进化出了一种简化的端粒酶，由一种小的非编码RNA组成，该RNA仅保留了端粒酶功能所必需的最小属性。简化的昆虫端粒酶展示了端粒酶核糖核蛋白复合物出现的一种合理进化途径，它起源于早期真核生物中与简单模板RNA成分相关的古老逆转录酶。
