Oral Presentation BACPATH 2019

Revealing the pathogen-specific RNA-binding proteome using UV-crosslinking (#17)

Brandon M Sy 1 , Vadim Shchepachev 2 , David Tollervey 2 , Jai J Tree 1
  1. School of Biotechnology and Biomolecular Sciences, UNSW, Sydney, NSW, Australia
  2. Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, Scotland, UK

RNA-binding proteins (RBPs) are key players in transcription, translation, and gene regulation in all organisms. High-throughput analysis of the RBPome has shown a surprisingly large number of RNA-protein interactions in model eukaryotes. In bacteria, RNA-binding proteins play critical roles in regulating gene expression and are required for pathogenesis. Until recently, all high-throughput studies to identify RNA-binding proteomes (RBPome) relied on purification of polyadenylated RNAs, and are not suitable for studying bacterial transcripts that lack a poly(A) tail. We have used a new technique termed total RNA-associated protein purification (TRAPP) to capture the RBPome of enterohaemorrhagic E. coli (EHEC). This method uses UV-crosslinking, silica beads, and organic extraction to selectively enrich crosslinked RNA-protein complexes. TRAPP identified 264 proteins that were at least twofold enriched in UV-crosslinked cultures and were enriched for proteins with known RNA-binding motifs. Of these, 28 were located on the pathogenicity islands of EHEC. The RNA-binding capabilities of a subset of proteins were assessed by radiolabelling the RNA 5’ ends of UV-crosslinked, affinity purified RNA-protein complexes. This demonstrated that 4 of 5 putative RBPs were able to bind RNA in vivo. EspY2 was found to bind RNA and is a type 3 secretion system effector protein that is translocated into host cells. Mutation of EspY2 has previously been shown to result in decreased host colonisation. Our results suggest that EspY2 may be a novel example of a bacterial RNA-binding protein that is injected into host cells to promote colonisation. Ongoing experiments are looking to identify the specific RNA targets of EspY2 in vivo.