GSE245749 TnpB homologs exapted from transposons are RNA-guided transcription factors

Contributors : Tanner Wiegand ; Florian T Hoffmann ; Matthew W Walker ; Stephen Tang ; Egill Richard ; Hoang C Le ; Chance Meers ; Samuel H SternbergSeries Type : Genome binding/occupancy profiling by high throughput sequencing ; Expression profiling by high throughput sequencing ; OtherOrganism : Enterobacter cloacae ; Enterobacter sp. BIDMC93 ; Escherichia coliTransposon-encoded tnpB and iscB genes encode RNA-guided DNA nucleases that promote their own selfish spread through targeted DNA cleavage and homologous recombination. These widespread gene families were repeatedly domesticated over evolutionary timescales, leading to the emergence of diverse CRISPR-associated nucleases including Cas9 and Cas12. 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 target conserved promoter regions of the genome, leading to potent gene repression in a mechanism akin to CRISPRi technologies invented by humans. Focusing on a TldR clade found broadly in Enterobacteriaceae, we discover that bacteriophages exploit the combined action of TldR and an adjacently encoded phage gene to alter the expression and composition ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencing Other Enterobacter cloacae Enterobacter sp. BIDMC93 Escherichia coli Source Type: research