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Structural RNA components supervise the sequential DNA cleavage in R2 retrotransposon. | LitMetric

Structural RNA components supervise the sequential DNA cleavage in R2 retrotransposon.

Cell

Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address:

Published: June 2023

AI Article Synopsis

  • Retroelements are key players in genome evolution and have potential uses as gene-editing tools; this study focuses on the eukaryotic R2 retrotransposon and its interactions with DNA and RNA.
  • The researchers used cryo-EM imaging along with biochemical and sequencing methods to identify two important DNA regions, Drr and Dcr, necessary for the retrotransposon's ability to recognize and cleave DNA.
  • They found that regulatory RNAs play a crucial role by influencing the timing of DNA cleavage and reverse transcription, leading to a better understanding of retrotransposon mechanics and possible applications in genetic reprogramming.

Article Abstract

Retroelements are the widespread jumping elements considered as major drivers for genome evolution, which can also be repurposed as gene-editing tools. Here, we determine the cryo-EM structures of eukaryotic R2 retrotransposon with ribosomal DNA target and regulatory RNAs. Combined with biochemical and sequencing analysis, we reveal two essential DNA regions, Drr and Dcr, required for 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 3'-tail. Removing 3' regulatory RNA by reverse transcription allows the association of 5' regulatory RNA and initiates the second-strand cleavage. Taken together, our work explains the DNA recognition and RNA supervised sequential retrotransposition mechanisms by R2 machinery, providing insights into the retrotransposon and application reprogramming.

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Source
http://dx.doi.org/10.1016/j.cell.2023.05.032DOI Listing

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