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

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

doi:10.1186/s13578-025-01367-0

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

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

Authors

Chongwen Cao^#¹, Weiyi Gong^#^{1

2}, Yuanlong Shuai^#^{1

2}, Sara Rasouli^#^{1

2}, Qianyun Ge¹, Anam Khan¹, Aleksandra Dakic³, Nagireddy Putluri⁴, Gennady Shvets⁵, Yun-Ling Zheng⁶, Danyal Daneshdoust^#¹, Rani Mahyoob^#¹, Jenny Li^#^{1

7}, Xuefeng Liu^#^{8

9}

Affiliations

¹ Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
² Biomedical Science Graduate Program, The Ohio State University, Columbus, OH, USA.
³ Division of Neuroscience, National Institute of Aging, Bethesda, MD, USA.
⁴ Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
⁵ School of Applied and Engineering Physics, Cornell University, Ithaca, NY, USA.
⁶ Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
⁷ Department of Pathology, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
⁸ Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA. xuefeng.liu@osumc.edu.
⁹ Departments of Pathology, Urology and Radiation Oncology, Wexner Medical Center, The Ohio State University, Columbus, OH, USA. xuefeng.liu@osumc.edu.

^# Contributed equally.

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.

Keywords: Non-canonical functions; Non-coding RNAs; TERC; TERT; Telomerase; Telomeres.

Publication types

Review

Abstract

Publication types

Grants and funding