端粒酶复合体非编码RNA组分（TERC）的典型和非典型功能

Canonical and non-canonical functions of the non-coding RNA component (TERC) of telomerase complex.

作者信息

Cao Chongwen, Gong Weiyi, Shuai Yuanlong, Rasouli Sara, Ge Qianyun, Khan Anam, Dakic Aleksandra, Putluri Nagireddy, Shvets Gennady, Zheng Yun-Ling, Daneshdoust Danyal, Mahyoob Rani, Li Jenny, Liu Xuefeng

机构信息

Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.

Biomedical Science Graduate Program, The Ohio State University, Columbus, OH, USA.

出版信息

Cell Biosci. 2025 Mar 1;15(1):30. doi: 10.1186/s13578-025-01367-0.

DOI:10.1186/s13578-025-01367-0

PMID:40025596

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11871756/

Abstract

The telomerase complex consists of a protein component (TERT), which has reverse transcriptase activity, and an RNA component (TERC), which serves as a template for telomere synthesis. Evidence is rapidly accumulating regarding the non-canonical functions of these components in both normal or diseased cells. An oligonucleotide-based drug, the first telomerase inhibitor, secured FDA approval in June 2024. We recently summarized the non-canonical functions of TERT in viral infections and cancer. In this review, we expand on these non-canonical functions of TERC beyond telomere maintenance. Specifically, we explore TERC's roles in cellular aging and senescence, immune regulation, genetic diseases, human cancer, as well as involvement in viral infections and host interactions. Finally, we discuss a transcription product of telomere repeats, TERRA, and explore strategies for targeting TERC as a therapeutic approach.

摘要

端粒酶复合物由具有逆转录酶活性的蛋白质成分（TERT）和作为端粒合成模板的RNA成分（TERC）组成。关于这些成分在正常细胞或患病细胞中的非经典功能的证据正在迅速积累。一种基于寡核苷酸的药物，即首个端粒酶抑制剂，于2024年6月获得了美国食品药品监督管理局（FDA）的批准。我们最近总结了TERT在病毒感染和癌症中的非经典功能。在本综述中，我们扩展了TERC除端粒维持之外的这些非经典功能。具体而言，我们探讨了TERC在细胞衰老和衰老、免疫调节、遗传疾病、人类癌症中的作用，以及其在病毒感染和宿主相互作用中的参与情况。最后，我们讨论了端粒重复序列的转录产物TERRA，并探索了以TERC为靶点的治疗策略。