# Identification of Factors Critical for SINE Retrotransposition

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $475,800

## Abstract

Abstract
 Short INterspersed Elements (SINEs) are mobile genetic elements that are present in all mammalian
genomes. Most mammalian SINEs can be subdivided into two general categories: (1) those derived from 7SL
signal recognition particle RNA (e.g., human Alu elements); and (2) those derived from transfer RNAs (e.g.,
canine SINEC_Cf elements). Alu and SINEC_Cf elements have had a major impact on genome evolution and
comprise an astounding ~11% and ~15% of human and canine genomic DNA, respectively. The vast majority
of SINEs have been rendered immobile by mutational processes; however, some human-specific Alu elements
and canine SINEC_Cf elements can mobilize to new genomic locations by a “copy and paste” mechanism
termed retrotransposition. To date, greater than 76 independent germline Alu retrotransposition events have
been implicated as the cause of human diseases, including cancer. SINEC_Cf retrotransposition events are
responsible for various diseases and phenotypic differences in canines. SINEs do not encode proteins; thus,
they are classified as `non-autonomous' retrotransposons. Previous studies, including our preliminary data,
demonstrate that a protein encoded by an autonomous Long INterspersed Element-1 (LINE-1) retrotransposon
(LINE-1 ORF2p) is required for Alu and SINEC_Cf element retrotransposition. We hypothesize that the
structure of Alu RNA, and by extension SINEC_Cf RNA, and unidentified host factor(s) allow these RNAs to
localize to the ribosome, where they can compete with the LINE-1 poly(A) tail for LINE-1 ORF2p binding to
promote their retrotransposition. Here, we propose to use a combination of molecular biological, evolutionary
inference, genetic, genomic, and biochemical approaches to: (1) use established RNA secondary structure
models, Illumina-based SHAPE-MaP chemical probing, and established cultured cell assays to uncover cis-
acting RNA structures and sequences required for human-specific Alu and SINEC_Cf retrotransposition; and
(2) exploit differences between HeLa cell isolates that differ in their ability to support Alu and SINEC_Cf
retrotransposition to identify host factor(s) critical for SINE retrotransposition. This proposal builds on
successful collaborations between the Moran and Kidd laboratories at the University of Michigan and will
combine the Moran laboratory's expertise in transposable element and RNA biology with the Kidd laboratory's
expertise in computational and statistical genomics and evolutionary biology to elucidate SINE
retrotransposition mechanisms.

## Key facts

- **NIH application ID:** 10095880
- **Project number:** 1R01GM140135-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Jeffrey M Kidd
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $475,800
- **Award type:** 1
- **Project period:** 2020-12-02 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10095880

## Citation

> US National Institutes of Health, RePORTER application 10095880, Identification of Factors Critical for SINE Retrotransposition (1R01GM140135-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10095880. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*