A degenerate telomerase RNA directs telomeric DNA synthesis in lepidopteran insects

• 成果类型: Article
• 署名作者: Chou, Yu - Shu; Logeswaran, Dhenugen; Chow, Chi - Nga; Dunn, Phoebe L.; Podlevsky, Joshua D.; Liu, Tianxiang; Akhter, Khadiza; Chen, Julian J. - L.
• 署名单位: Arizona State University; Arizona State University-Tempe; Arizona State University; Arizona State University-Tempe; United States Department of Energy (DOE); Sandia National Laboratories
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14803
• DOI: 10.1073/pnas.2424443122
• 发表日期: 2025-02-28
• 关键词: template-boundary definition; catalytic subunit; structural basis; tetrahymena; domain; binding; pseudoknot; yeast; retrotransposons; contributes

摘要

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 Spodoptera frugiperda (fall army- worm) and identify a copurified 135- nucleotide telomerase RNA (TR) component. This miniature S. frugiperda 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 S. frugiperda 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 (M7G) 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.