YTHDC1 Orchestrates Telomerase Assembly via Scaffold-Mediated TERT-TERC Interaction.

ABSTRACT: Telomerase RNA (TERC) is subject to various modifications, yet the implications of these modifications for telomerase biology remain largely unexplored. In this study, we conducted a comprehensive mapping of N6-Methyladenosine (m6A) modifications within TERC RNA and elucidated their regulatory role in telomerase function. Our findings demonstrate that TERC undergoes methylation at adenosine residues A111 and A435 by METTL3. A deficiency in TERC m6A, which is also linked to various human telomerase disease-related mutations and deletions, significantly reduces telomerase activity and telomere length by disrupting the association between TERC and TERT. Mechanistically, YTHDC1 was identified as a scaffold facilitating the interaction between TERT and TERC, binding to TERT while recognizing m6

SUBMITTER: Cheng X 

PROVIDER: S-EPMC12745060 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature