Telomerase RNA structural heterogeneity in living human cells detected by DMS-MaPseq.

ABSTRACT: Biogenesis of human telomerase requires its RNA subunit (hTR) to fold into a multi-domain architecture that includes the template-pseudoknot (t/PK) and the three-way junction (CR4/5). These hTR domains bind the telomerase reverse transcriptase (hTERT) protein and are essential for telomerase activity. Here, we probe hTR structure in living cells using dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) and ensemble deconvolution analysis. Approximately 15% of the steady state population of hTR has a CR4/5 conformation lacking features required for hTERT binding. The proportion of hTR CR4/5 folded into the primary functional conformation is independent of hTERT expression levels. Mutations that stabilize the alternative CR4/5 conformation are detrimental to telomerase assembl

SUBMITTER: Forino NM 

PROVIDER: S-EPMC11754830 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature