# Biology and utilization of R2 retrotransposons

**Authors:** Shengqiu Luo, Qicheng Chen, Yangcan Chen, Wei Li

PMC · DOI: 10.1080/15476286.2025.2521890 · 2025-06-25

## TL;DR

This paper reviews R2 retrotransposons, their unique ability to insert into specific genomic sites, and their potential as tools for genome engineering.

## Contribution

The paper highlights recent advances in using R2 retrotransposons for targeted gene integration and their potential as biotechnological tools.

## Key findings

- R2 retrotransposons insert into ribosomal DNA using a precise mechanism called target-primed reverse transcription.
- The R2-encoded protein has multiple functions including reverse transcriptase and endonuclease activities.
- R2 elements are being explored as novel tools for targeted gene integration in genome engineering.

## Abstract

R2 elements serve as a class of non-long terminal repeat (non-LTR) retrotransposons found in animal genomes that specifically insert into the ribosomal DNA (rDNA) sequences of host genomes. Each R2 element contains a single open reading frame (ORF) encoding a multifunctional protein with nucleic acid-binding, reverse transcriptase, and endonuclease activities, enabling specific genomic integration via a mechanism called target-primed reverse transcription (TPRT). As a classical model for studying retrotransposition mechanisms, R2 elements possess unique biological properties and precise integration capabilities, which have inspired novel genome engineering strategies. In this review, we summarize the components and integration mechanisms of R2 retrotransposons and highlight the recent advances in employing these mobile elements for targeted gene integration. Finally, we present future directions for the utilization of R2 retrotransposons as novel biotechnological tools.

## Full-text entities

- **Genes:** ENOSF1 (enolase superfamily member 1) [NCBI Gene 55556] {aka FUCD, RTS, TYMSAS}, PDSS1 (decaprenyl diphosphate synthase subunit 1) [NCBI Gene 23590] {aka COQ1, COQ10D2, COQ1A, DPS, SPS, TPRT}, ZNF274 (zinc finger protein 274) [NCBI Gene 10782] {aka HFB101, ZF2, ZKSCAN19, ZSCAN51}, MYB (MYB proto-oncogene, transcription factor) [NCBI Gene 4602] {aka Cmyb, c-myb, c-myb_CDS, efg}
- **Chemicals:** R2Bm (-), nucleoside (MESH:D009705)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Bombyx mori (domestic silkworm, species) [taxon 7091], Homo sapiens (human, species) [taxon 9606], Adineta vaga (species) [taxon 104782], Drosophila melanogaster (fruit fly, species) [taxon 7227], Oryzias latipes (Japanese medaka, species) [taxon 8090], Calliphora vicina (urban bluebottle blowfly, species) [taxon 7373], Hepatitis delta virus (no rank) [taxon 12475], Danio rerio (leopard danio, species) [taxon 7955]
- **Cell lines:** Huh7 — Homo sapiens (Human), Adult hepatocellular carcinoma, Cancer cell line (CVCL_0336), R2Ol — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_M128), hTERT RPE-1 — Homo sapiens (Human), Telomerase immortalized cell line (CVCL_4388)

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12203849/full.md

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Source: https://tomesphere.com/paper/PMC12203849