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PreprintCited by 51Chromosomal and Genetic VariationsCRISPR and Genetic EngineeringRNA Research and Splicing

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Structural RNA components supervise the sequential DNA cleavage in R2 retrotransposon

Open access
Deng, Pujuan, Tan, Shun-Qing, Yang, Qi-Yu, Zhu, Han-Zhou, Sun, Lei, Bao, Zhangbin, Lin, Yi, Zhang, Qiangfeng Cliff, Wang, Jia, Liu, Jun-Jie Gogo·2023·Cell
DOI 10.1101/2023.04.07.536001

Preprint — published as 10.1016/j.cell.2023.05.032

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Abstract

Summary: Retroelements are the widespread jumping elements considered as major drivers for genome evolution, which can also be repurposed as gene-editing tools. Here, we determined the cryo-EM structures of eukaryotic R2 retrotransposon with ribosomal DNA target and regulatory RNAs. Combined with biochemical and sequencing analysis, we revealed two essential DNA regions, Drr and Dcr, required for R2 recognition and cleavage. The association of 3’ regulatory RNA with R2 protein accelerates the first-strand cleavage, blocks the second-strand cleavage, and initiates the reverse transcription starting from the polyA tail. Removing 3’ regulatory RNA by reverse transcription allows the association of 5’ regulatory RNA and initiates the second-strand cleavage. Our work explained the DNA recognition and supervised sequential retrotransposition mechanisms by R2 machinery, providing novel insights into the retrotransposon and application reprogramming.

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Metadata

Authors
Deng, P., Tan, S.-Q., Yang, Q.-Y., Zhu, H.-Z., Sun, L., Bao, Z., Lin, Y., Zhang, Q. C., Wang, J., & Liu, J.-J. G.
Affiliations
  • Center for Life Sciences (CN)
  • Shandong University (CN)
  • Tsinghua University (CN)
Corresponding author
Wang, Jia
ORCID
Venue
Cell
Publisher
openRxiv
Published
2023-04-07
Volume
186
Issue
13
Pages
2865-2879.e20
ISSN
0092-8674 (ISSN-L)
DOI
10.1101/2023.04.07.536001
OpenAlex
W4380154105
Cited by
51
References
1
Citations by year
2026: 18 · 2025: 14 · 2024: 15 · 2023: 4
FWCI
8.04
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
Funders
Tsinghua University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
R2 retrotransposon, retrotransposition, DNA cleavage, reverse transcription initiation, DNA recognition, cryo-EM structure, genome evolution
MeSH terms
RNA-Directed DNA Polymerase, RNA, Retroelements, Reverse Transcription, DNA Cleavage

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