# Expression and Impact of Interspersed Repeats

> **NIH NIH R01** · DANA-FARBER CANCER INST · 2022 · $354,000

## Abstract

Summary
Endogenous retroviruses and related transposable elements make up much of our genome, and active forms
persist as long interspersed element-1 (LINE-1, L1) retrotransposons and the elements it mobilizes. These are
self-propagating sequences which copy themselves through the reverse transcription of RNA intermediates.
We have developed elaborate mechanisms to silence their transcription and limit their proliferation. However, a
careful approach to RNAseq analysis reveals that that a subset of individual transposon loci (ITL) escape
silencing and are transcriptionally active. In a survey of normal human cells, we identify both constitutive and
variably expressed ITL. Our ability to measure these transcripts provides a unique opportunity to examine this
host-pathogen relationship and its role in gene regulation. Here, we propose to test the hypothesis that
retroelement expression (or lack thereof) is an indicator of specific regulatory mechanisms with cis-acting
effects on neighboring genes. We propose to define the landscape of expressed retrotransposons in humans;
demonstrate molecular mechanisms of transcriptional silencing and escape; and probe how these mechanisms
affect gene expression in human ‘epigenetic’ diseases. We will use genome editing strategies to test whether
altering ITL sequences affects neighboring gene expression. Finally, we will develop approaches to study
prevalent, highly-expressed short interspersed elements (SINEs) to assess their potential for
retrotransposition, determine whether they are targets of RNA editing or dsRNA sensing pathways, and test
their interactions with cellular mRNAs in trans. These studies will be among the first to delve into the
expression and function of a broad range of retrotransposon intermediates in human cells.

## Key facts

- **NIH application ID:** 10409704
- **Project number:** 5R01GM130680-04
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** KATHLEEN H BURNS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $354,000
- **Award type:** 5
- **Project period:** 2019-07-24 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10409704

## Citation

> US National Institutes of Health, RePORTER application 10409704, Expression and Impact of Interspersed Repeats (5R01GM130680-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10409704. Licensed CC0.

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