Integration, regulation, and long-term stability of R2 retrotransposons
Open accessAbstract
R2 elements are sequence specific non-LTR retrotransposons that exclusively insert in the 28S rRNA genes of animals. R2s encode an endonuclease that cleaves the insertion site and a reverse transcriptase that uses the cleaved DNA to prime reverse transcription of the R2 transcript, a process termed target primed reverse transcription. Additional unusual properties of the reverse transcriptase as well as DNA and RNA binding domains of the R2 encoded protein have been characterized. R2 expression is through co-transcription with the 28S gene and self-cleavage by a ribozyme encoded at the R2 5′ end. Studies in laboratory stocks and natural populations of Drosophila suggest that R2 expression is tied to the distribution of R2-inserted units within the rDNA locus. Most individuals have no R2 expression because only a small fraction of their rRNA genes need to be active, and a contiguous region of the locus free of R2 insertions can be selected for activation. However, if the R2-free region is not large enough to produce sufficient rRNA, flanking units - including those inserted with R2 - must be activated. Finally, R2 copies rapidly turnover within the rDNA locus, yet R2 has been vertically maintained in animal lineages for hundreds of millions of years. The key to this stability is R2's ability to remain dormant in rDNA units outside the transcribed regions for generations until the stochastic nature of the crossovers that drive the concerted evolution of the rDNA locus inevitably reshuffle the inserted and uninserted units, resulting in transcription of the R2-inserted units.
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Some rDNA units contain R1/R2 insertions shortened to varying degrees from the 5′-end, formed due to abortive reverse transcription.
“Some rDNA units contain R1/R2 insertions shortened to varying degrees from the 5′-end, formed due to abortive reverse transcription (30,41).”
From Impaired function of rDNA transcription initiation machinery leads to derepression of ribosomal genes with insertions of R2 retrotransposon (2022) · cites this paper as [30]
The section “R2 copies are rapidly gained and lost from rDNA loci” describes R2 insertions with 5′ truncations of varying lengths. “Current model of R2 integration” says these arise when reverse transcriptase does not reach the 5′ end of the RNA template. The Introduction places R1 insertions in rDNA, but our copy does not establish the same truncation mechanism for R1. (LLM, conf=0.88)
Experimental — accuracy not yet measuredFull-length R2 insertions encode a ribozyme that releases the 5′-end of the R2 transcript from the upstream 28S rRNA sequence during the autocatalytic reaction.
“Full-length R2 insertions encode a ribozyme, which releases the 5′-end of the R2 transcript from the upstream 28S rRNA sequence during the autocatalytic reaction (Figure 1A)”
From Impaired function of rDNA transcription initiation machinery leads to derepression of ribosomal genes with insertions of R2 retrotransposon (2022) · cites this paper as [30]
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Origin and evolution of retroelements based upon their reverse transcriptase sequences
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Self-citationRECOMBINATIONAL CONTROLS OF rDNA REDUNDANCY IN <i>DROSOPHILA</i>
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“The chromatin associated with R2 insertions contained the typical epigenetic marks linked to heterochromatin (106).”
BackgroundResultInfluentialSelf-citationZhou, J., & Eickbush, T. H. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000386 · Cited by 30 · see citing works
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Luo, Y., Fefelova, E., Ninova, M., Chen, Y.-C. A., & Aravin, A. A. (2020) · eLife · doi:10.7554/elife.52416 · Cited by 19 · see citing works
Fefelova, E. A., Pleshakova, I. M., Mikhaleva, E. A., Pirogov, S. A., Poltorachenko, V. A., Abramov, Y. A., Romashin, D. D., Shatskikh, A. S., Blokh, R. S., Gvozdev, V. A., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkab1276 · Cited by 15 · see citing works
“R2 insert into a strictly defined site in the rDNA sequence located 2651 bp after the beginning of the 28S rRNA and R1 elements are integrated 74 bp downstream of the R2 insertion site (30).”
BackgroundInfluentialThe retrotransposon <i>R2</i> maintains <i>Drosophila</i> ribosomal DNA repeats
Nelson, J. O., Slicko, A., & Yamashita, Y. M. (2021) · doi:10.1101/2021.07.12.451825 · Cited by 7 · see citing works
- Authors
- Eickbush, T. H., & Eickbush, D. G.
- Affiliations
- University of Rochester (US)
- Venue
- Microbiology Spectrum
- Publisher
- American Society for Microbiology
- Published
- 2015-04-02
- Volume
- 3
- Issue
- 2
- Pages
- MDNA3-0011
- ISSN
- 2165-0497 (ISSN-L)
- PMC
- PMC4498411
- OpenAlex
- W858000480
- Cited by
- 81
- References
- 8
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 19 · 2023: 8 · 2022: 8 · 2021: 6 · 2020: 3 · 2019: 9 · 2018: 4 · 2017: 3 · 2016: 1 · 2015: 1
- FWCI
- 0.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Microbiology Spectrum (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM42790, R01GM042790)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- R2 retrotransposon, non-LTR retrotransposons, 28S rRNA gene, rDNA locus, target-primed reverse transcription, Drosophila, transposable element regulation, concerted evolution, transposon insertion
- MeSH terms
- Animals, Binding Sites, DNA, Ribosomal, Gene Expression Regulation, Recombination, Genetic, RNA-Directed DNA Polymerase, RNA, Ribosomal, 28S, Mutagenesis, Insertional, Short Interspersed Nucleotide Elements, Genomic Instability, Reverse Transcription
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