# The roles of telomerase and non-coding RNA in cancer

> **NIH NIH K00** · UNIVERSITY OF COLORADO · 2021 · $105,061

## Abstract

Project Summary
The predoctoral phase of this proposal will focus on the biochemical and biophysical studies of the enzyme
telomerase. Telomerase is a ribonucleoprotein that maintains telomere lengths in rapidly dividing cells, thereby
counteracting the chromosome shortening that is inherent to each round of cell division. Without telomerase,
cells undergo senescence when telomere lengths become critically short. Telomerase is upregulated in about
90% of cancers due to the need for telomere maintenance in rapidly dividing cells making it an attractive drug
target. Cancer therapeutics that target active telomerase directly have remained elusive however. The structure
and function of human telomerase is still poorly understood, and any new insight would greatly benefit the
development of novel cancer therapeutics. The dissertation project focuses on using single molecule techniques
to study the conformation and dynamics of human telomerase. The minimal human telomerase is composed of
two subunits, a protein component (TERT) that contains four evolutionarily conserved domains and an RNA
component (TER) which contains the integral non-coding RNA template from which telomeres are reverse
transcribed. Telomerase is unique in its ability to reverse transcribe multiple telomere repeats during a single
DNA binding event, but the details of how telomerase maintain this processive action remains poorly understood.
Additionally, details regarding how TERT and TER interact during catalysis, and how individual TERT domains
regulate telomerase dynamics, remain unknown. Specifically, knowledge about the function and dynamics of
two TERT domains, the Telomerase Essential N-terminal (TEN) domain and the C-terminal extension (CTE)
remain especially poorly understood. This project will test the hypothesis that the TEN and CTE domains drive
the processive action of telomerase via coordinated dynamic rearrangement of the telomere/template hybrid into
its initial bound state at the end of each telomere repeat addition event. Single molecule Förster Resonance
Energy Transfer (smFRET), in combination with a novel protein labeling scheme, will be used to probe the
conformation and dynamics of these domains during different functional states. In addition, computational
modeling in collaboration with the Das lab at Stanford will enable the construction of a refined working model of
human telomerase during catalysis. Completion of this proposal will aid in the development of telomerase
targeted cancer therapeutics. In addition, this proposal will facilitate the smooth transition from studying RNP
structure and function during the predoctoral phase, to the study of long non-coding RNA (lncRNA) structure and
its roles in the development of cancer during the postdoctoral phase. The techniques and approaches learned
during the dissertation research will lend themselves perfectly to the study of RNA structure, which to date has
remained a difficult area to study. The timing of th...

## Key facts

- **NIH application ID:** 10218067
- **Project number:** 5K00CA212439-06
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Linnea Jansson-Fritzberg
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $105,061
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10218067

## Citation

> US National Institutes of Health, RePORTER application 10218067, The roles of telomerase and non-coding RNA in cancer (5K00CA212439-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10218067. Licensed CC0.

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