Transposon-associated TnpB is a programmable RNA-guided DNA endonuclease

• DOI: 10.1038/s41586-021-04058-1
• Publication Date: 2021-10-07T16:04:41Z
• Authors: Tautvydas Karvelis; Gytis Druteika; Greta Bigelyte; Karolina Budre; Rimante Zedaveinyte; Arunas Silanskas; Darius Kazlauskas; Česlovas Venclovas; Virginijus Siksnys
• Keywords: Transposase; Transposition (logic); Tn3 transposon; Retrotransposon; Extrachromosomal DNA

Abstract Transposition has a key role in reshaping genomes of all living organisms 1 . Insertion sequences IS200/IS605 and IS607 families 2 are among the simplest mobile genetic elements contain only genes that required for their transposition its regulation. These encode tnpA transposase, which is essential mobilization, often carry an accessory tnpB gene, dispensable transposition. Although TnpA transposon mobilization well documented, function TnpB remained largely unknown. It had been suggested regulation transposition, although no mechanism this established 3–5 A bioinformatic analysis indicated might be predecessor CRISPR–Cas9/Cas12 nucleases 6–8 However, biochemical activities have ascribed to TnpB. Here we show Deinococcus radiodurans ISDra2 RNA-directed nuclease guided by RNA, derived from right-end element transposon, cleave DNA next 5′-TTGAT transposon-associated motif. We also could reprogrammed target sites human cells. Together, study expands our understanding mechanisms highlighting experimentally confirms functional progenitor CRISPR–Cas establishes as prototype new system genome editing.