Emergence of RNA-guided transcription factors via domestication of transposon-encoded TnpB nucleases.

ABSTRACT: Transposon-encoded tnpB genes encode RNA-guided DNA nucleases that promote their own selfish spread through targeted DNA cleavage and homologous recombination^1-4. This widespread gene family was repeatedly domesticated over evolutionary timescales, leading to the emergence of diverse CRISPR-associated nucleases including Cas9 and Cas12^5,6. We set out to test the hypothesis that TnpB nucleases may have also been repurposed for novel, unexpected functions other than CRISPR-Cas. Here, using phylogenetics, structural predictions, comparative genomics, and functional assays, we uncover multiple instances of programmable transcription factors that we name TnpB-like nuclease-dead repressors (TldR). These proteins employ naturally occurring guide RNAs to specifically t

SUBMITTER: Wiegand T 

PROVIDER: S-EPMC10705468 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature