# Structural Biology of Retrotransposition (Equipment Supplement)

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $113,078

## Abstract

PROJECT SUMMARY/ABSTRACT
Structural biology of retrotransposition. Non-long terminal repeat (non-LTR) retroelements are mobile genetic
elements that are able to copy and paste themselves into new locations in DNA genomes using a reverse
transcriptase and an RNA intermediate. These retroelements comprise at least 46% of the human genome
and little is known about their precise mechanism of integration into double stranded DNA. LINE elements are
a particularly abundant class of retroelements in the human genome and have large effects on gene
expression through insertion near transcription promoters. In addition, aberrant retrotransposition by LINE
elements can result in the development of cancer through disruption of tumor suppressor genes. Despite more
than 30 years of study, there is no atomic model that would explain the mechanism of retrotransposition at the
molecular level. This is due to the fact that LINE elements are difficult targets for structure determination
because they exhibit very low levels of retrotransposition in vitro. Group II introns are thought to be the
ancestors of eukaryotic non-LTR retroelements, such as the LINE elements found in humans. Group II
retroelements are a more tractable model system for structure determination due to their stability and high
activity of retrotransposition in vitro. To gain structural insight into retrotransposition, we aim to use single-
particle cryo-EM to solve high-resolution structures of a group II intron retroelement. Specifically, we will obtain
structures of the retroelement during the different stages of retrotransposition into dsDNA. We will use a
combination of biochemical, genetic, and structural approaches to: 1) Determine the structure of a free group
II intron retroelement. 2) Determine the mechanism of integration into a target double-stranded DNA. This is
expected to have direct parallels with retrotransposition catalyzed by mammalian retroelements. We will
capture different stages of retrotransposition to create a `molecular movie' of the entire process. This will
represent the first atomic model of retrotransposition.

## Key facts

- **NIH application ID:** 10132697
- **Project number:** 3R01GM123275-04S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Navtej Singh Toor
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $113,078
- **Award type:** 3
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132697

## Citation

> US National Institutes of Health, RePORTER application 10132697, Structural Biology of Retrotransposition (Equipment Supplement) (3R01GM123275-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10132697. Licensed CC0.

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