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Transposon-associated TnpB is a programmable RNA-guided DNA endonuclease
- Source :
- Nature, Berlin : Nature research, 2021, vol. 599, p. 692-696
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Transposition has a key role in reshaping genomes of all living organisms1. Insertion sequences of IS200/IS605 and IS607 families2 are among the simplest mobile genetic elements and contain only the genes that are required for their transposition and its regulation. These elements encode tnpA transposase, which is essential for mobilization, and often carry an accessory tnpB gene, which is dispensable for transposition. Although the role of TnpA in transposon mobilization of IS200/IS605 is well documented, the function of TnpB has remained largely unknown. It had been suggested that TnpB has a role in the regulation of transposition, although no mechanism for this has been established3–5. A bioinformatic analysis indicated that TnpB might be a predecessor of the CRISPR–Cas9/Cas12 nucleases6–8. However, no biochemical activities have been ascribed to TnpB. Here we show that TnpB of Deinococcus radiodurans ISDra2 is an RNA-directed nuclease that is guided by an RNA, derived from the right-end element of a transposon, to cleave DNA next to the 5′-TTGAT transposon-associated motif. We also show that TnpB could be reprogrammed to cleave DNA target sites in human cells. Together, this study expands our understanding of transposition mechanisms by highlighting the role of TnpB in transposition, experimentally confirms that TnpB is a functional progenitor of CRISPR–Cas nucleases and establishes TnpB as a prototype of a new system for genome editing.
- Subjects :
- Transposable element
CRISPR-Associated Proteins
Computational biology
Biology
Transposition (music)
chemistry.chemical_compound
Genome editing
Escherichia coli
Deoxyribonuclease I
Humans
Nucleotide Motifs
Insertion sequence
Gene
Transposase
Gene Editing
Nuclease
Multidisciplinary
Base Sequence
HEK293 Cells
chemistry
TnpB
CRISPR-Cas
transposition
DNA Transposable Elements
biology.protein
RNA
Deinococcus
CRISPR-Cas Systems
DNA
Subjects
Details
- ISSN :
- 14764687 and 00280836
- Volume :
- 599
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....51bf5a25af0ec559da51d1bb5a09fafe