# Functional characterization of the telomere repeat containing RNA, TERRA, in telomere maintenance

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $371,250

## Abstract

Mammalian telomeres are sequential hexameric TTAGGG DNA repeats that cap the
ends of linear chromosomes. Structurally, the telomeric DNA forms a lariat, or T-loop, at the end
of each chromosome to shield the ends of linear chromosomes from degradation and/or
illegitimate recombination. The six-subunit protein complex shelterin binds and protects
telomeric DNA with sequence specificity functioning to both inhibit the DNA damage response
and regulate T-loop formation. Defects in shelterin function lead to telomere instability and
contribute to both premature aging and the progression towards cancer. Recently this
protective cap at telomere ends has expanded beyond shelterin to include the telomere repeat-
containing RNA, TERRA. TERRA is expressed in several eukaryotes including plants, yeast,
fish, and mammals. In human cells, TERRA is transcribed from the C-strand within the
subtelomeric region and transcription elongation extends into the telomere repeats generating a
transcript between 200bp and 9kb. TERRA is localized within the nucleus and associates with
both the telomeric DNA and telomere associated proteins. The discovery of this long non-
coding RNA, expressed from a region once considered transcriptionally silent, suggests that
there is still much to learn about the mechanisms of telomere maintenance and the role these
mechanisms play in the development of cancer. In previous studies, we have demonstrated
that TERRA is cell cycle regulated, and that this regulation drives a molecular switch
coordinating telomere replication with telomere end protection in vitro. While these studies were
among the first to demonstrate a functional requirement for TERRA in telomere maintenance,
exactly how TERRA functions to mediate these process in mammalian cells is still unclear.
These studies have been limited, in part, by an inability to manipulate endogenous TERRA
transcript levels. To overcome this challenge, we have designed a Clustered Regularly
Interspaced Short Palindromic Repeat (CRISPR) system that allows us to manipulate gene
expression from the endogenous TERRA promoter. Therefore, the goal of this proposal is to
further define the function of TERRA in regulation of telomere stability and ultimately,
understand how defects in TERRA function contribute to the development of cancer.

## Key facts

- **NIH application ID:** 9861236
- **Project number:** 5R01CA214880-04
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** RACHEL L. FLYNN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $371,250
- **Award type:** 5
- **Project period:** 2017-03-17 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9861236

## Citation

> US National Institutes of Health, RePORTER application 9861236, Functional characterization of the telomere repeat containing RNA, TERRA, in telomere maintenance (5R01CA214880-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9861236. Licensed CC0.

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