RNA modification in immune evasion and immune recognition

• Applicant: Professor Dr. Stefan Bauer
• Subject Area: Immunology
• Term: from 2009 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 115690894

• Final Report Year: 2015

Final Report Abstract

RNA has various immunoregulatory properties. Bacterial and viral RNA triggers pattern recognition receptors such as Toll-like receptor (TLR)-7, TLR8, TLR13 or RNA-helicases such as RIG-I. In contrast, endogenous self-RNA is usually not immunostimulatory due to RNA-modifications (e.g. base or ribose methylation) but gains immunostimulatory capacity upon RNase digestion. In this project, we addressed the question if RNA methylation is exploited by pathogens to evade immune recognition via pattern recognition receptors. We could demonstrate that 2’O methylation of a conserved guanosine in transfer RNA and a specific adenosine base methylation in bacterial 23s ribosomal RNA negatively modulates RNA immune recognition via TLR7 or TLR13, respectively. These observations support the view that specific RNA modifications may help to evade immune recognition by certain TLRs. In addition, we have identified a RNA sequence from the ITS2 region of human ribosomal RNA that efficiently activates RIG-I in a 5’-triphosphate independent manner. This observation defines a new ligand for RIG-I with the potential as immune adjuvant or therapeutic agent.

Publications

• 2012. The 2'-O-methylation status of a single guanosine controls transfer RNA-mediated Toll-like receptor 7 activation or inhibition. The Journal of experimental medicine 209:235-241
  Jockel, S., G. Nees, R. Sommer, Y. Zhao, D. Cherkasov, H. Hori, G. Ehm, M. Schnare, M. Nain, A. Kaufmann, and S. Bauer
  
• 2012. TLR13 recognizes bacterial 23S rRNA devoid of erythromycin resistance-forming modification. Science (New York, N.Y.) 337:1111- 1115
  Oldenburg, M., A. Kruger, R. Ferstl, A. Kaufmann, G. Nees, A. Sigmund, B. Bathke, H. Lauterbach, M. Suter, S. Dreher, U. Koedel, S. Akira, T. Kawai, J. Buer, H. Wagner, S. Bauer, H. Hochrein, and C.J. Kirschning
  
• 2014. Detection of RNA modifications by HPLC analysis and competitive ELISA. Methods in molecular biology (Clifton, N.J.) 1169:3-14
  Nees, G., A. Kaufmann, and S. Bauer
  
• 2015. A single naturally occurring 2'-O-methylation converts a TLR7- and TLR8-activating RNA into a TLR8-specific ligand. PloS one 10:e0120498
  Jung, S., T. von Thulen, V. Laukemper, S. Pigisch, D. Hangel, H. Wagner, A. Kaufmann, and S. Bauer