Abstract

Telomerase RNA (TR) is a noncoding RNA essential for the function of telomerase ribonucleoprotein. TRs from vertebrates, fungi, ciliates, and plants exhibit extreme diversity in size, sequence, secondary structure, and biogenesis pathway. However, the evolutionary pathways leading to such unusual diversity among eukaryotic kingdoms remain elusive. Within the metazoan kingdom, the study of TR has been limited to vertebrates and echinoderms. To understand the origin and evolution of TR across the animal kingdom, we employed a phylogeny-guided, structure-based bioinformatics approach to identify 82 novel TRs from eight previously unexplored metazoan phyla, including the basal-branching sponges. Synthetic TRs from two representative species, a hemichordate and a mollusk, reconstitute active telomerase in vitro with their corresponding telomerase reverse transcriptase components, confirming that they are authentic TRs. Comparative analysis shows that three functional domains, template-pseudoknot (T-PK), CR4/5, and box H/ACA, are conserved between vertebrate and the basal metazoan lineages, indicating a monophyletic origin of the animal TRs with a snoRNA-related biogenesis mechanism. Nonetheless, TRs along separate animal lineages evolved with divergent structural elements in the T-PK and CR4/5 domains. For example, TRs from echinoderms and protostomes lack the canonical CR4/5 and have independently evolved functionally equivalent domains with different secondary structures. In the T-PK domain, a P1.1 stem common in most metazoan clades defines the template boundary, which is replaced by a P1-defined boundary in vertebrates. This study provides unprecedented insight into the divergent evolution of detailed TR secondary structures across broad metazoan lineages, revealing ancestral and later-diversified elements.

中文翻译：

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动物端粒酶RNA的单系起源和不同进化。

摘要

端粒酶 RNA (TR) 是一种非编码 RNA，对端粒酶核糖核蛋白的功能至关重要。来自脊椎动物、真菌、纤毛虫和植物的 TRs 在大小、序列、二级结构和生物发生途径方面表现出极大的多样性。然而，导致真核生物界如此不寻常的多样性的进化途径仍然难以捉摸。在后生动物界，TR 的研究仅限于脊椎动物和棘皮动物。为了了解整个动物王国中 TR 的起源和进化，我们采用了一种系统发育指导的、基于结构的生物信息学方法，从 8 个以前未探索的后生动物门中识别出 82 个新的 TR，包括基底分支海绵。来自两个代表性物种，半脊索动物和软体动物的合成 TR，用相应的端粒酶逆转录酶成分在体外重建活性端粒酶，确认它们是真实的 TR。比较分析表明，模板假结（T-PK）、CR4/5 和框 H/ACA 这三个功能域在脊椎动物和基底后生动物谱系之间是保守的，表明具有 snoRNA 相关的动物 TRs 的单系起源生物发生机制。尽管如此，沿不同动物谱系的 TR 在 T-PK 和 CR4/5 域中进化出不同的结构元素。例如，棘皮动物和原生动物的 TRs 缺乏典型的 CR4/5，并且具有独立进化的具有不同二级结构的功能等效域。在 T-PK 域中，大多数后生动物进化枝中常见的 P1.1 茎定义了模板边界，它被脊椎动物中 P1 定义的边界所取代。这项研究为跨广泛的后生动物谱系的详细 TR 二级结构的不同进化提供了前所未有的洞察力，揭示了祖先和后来多样化的元素。