# Structure and Dynamics of the Telomerase Ribonucleoprotein

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2020 · $396,895

## Abstract

Project Summary
The telomerase ribonucleoprotein (RNP) is required for maintaining telomeres, the specialized nucleoprotein
structures that protect eukaryotic chromosome ends from aberrant processing and deleterious end-to-end fu-
sion events. Telomerase catalyzes processive extension of telomere DNA via a unique catalytic mechanism
that requires a strong functional interdependence of the telomerase RNA, telomerase reverse transcriptase
(TERT), and several additional protein subunits. The primary objective of this proposal is to elucidate how
conserved structural RNA and protein domains coordinate the processes of telomerase RNP assembly, cataly-
sis, and recruitment to telomeres. To address this goal, we will utilize a multi-faceted experimental strategy that
combines single-molecule biophysical techniques paired with computational, biochemical, and high-resolution
structural approaches. We will study human telomerase and the enzyme from the model system Tetrahymena
thermophila. In aim 1, we will employ biochemical structure probing, single-molecule Förster resonance energy
transfer (smFRET), and x-ray crystallography to analyze structural intermediate states adopted by telomerase
RNA and TERT during the RNP assembly pathway. In aim 2, we will use smFRET and a novel telomerase ac-
tivity detection method to investigate conformational dynamics of protein and RNA domains that drive telomer-
ase function. In aim 3, we will study the dynamic DNA handling properties of the telomerase enzyme. These
experiments will focus on the molecular mechanisms for telomerase recruitment to telomeres as well as under-
standing how the intrinsic folding properties of telomere DNA regulate telomerase catalysis.

## Key facts

- **NIH application ID:** 9818378
- **Project number:** 2R01GM095850-10
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Michael D Stone
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $396,895
- **Award type:** 2
- **Project period:** 2010-12-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9818378

## Citation

> US National Institutes of Health, RePORTER application 9818378, Structure and Dynamics of the Telomerase Ribonucleoprotein (2R01GM095850-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9818378. Licensed CC0.

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