How to shirk recognition of RNA by TLR7
Abstract
Among the various sensors of the innate immune system that recognize nucleic acids, TLR7 is an endosomal Pattern-Recognition Receptor (PRR) destined to recognize hypomodified RNA as a pathogen-associated molecular patterns (PAMPs). TLR7 is tasked to discriminate "self" from "foreign" RNA, and the molecular details of the RNA that allow such discrimination are in the centre of our research efforts. From comparison synthetic unmodified RNAs to prokaryotic and eukaryotic RNAs, it became clear that chemical alterations such as native post-transcriptional, or synthetic modifications are the decisive parameter that governs RNA mediated TLR7 response. Using a combination of what is commonly known as RNA "microsurgery" and chemical synthesis, we have engineered several series of differentially modified RNAs. Testing the interferon response of dendritic cells to these RNAs has revealed different modifications that are capable of attenuating the TLR7-mediated response. Foremost among these are different ribose methylations, which can now be mapped in the epitranscriptome by RNA Seq approaches. A possible conjecture of these findings implies ribose methylation as an inducible means for immune evasion by microbial pathogens.