Structural RNA components supervise the sequential DNA cleavage in R2 retrotransposon.
R2 retrotransposon
RNA structure
cryo-EM
non-LTR
nuclease
retroelement
retrotransposition
reverse transcription
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
22 06 2023
22 06 2023
Historique:
received:
25
02
2023
revised:
14
03
2023
accepted:
20
05
2023
medline:
26
6
2023
pubmed:
11
6
2023
entrez:
10
6
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37301196
pii: S0092-8674(23)00584-6
doi: 10.1016/j.cell.2023.05.032
pii:
doi:
Substances chimiques
Retroelements
0
RNA
63231-63-0
RNA-Directed DNA Polymerase
EC 2.7.7.49
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2865-2879.e20Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.