Abstracts (complete list) - Wissenschaft Online

Florian Eberle, Mehtap Sirin, Klaus Heeg, Alexander Dalpke
Relevance of RNA-mediated immunostimulation for RNA-
Interference (RNAi)
Double-stranded RNAs can regulate endogenous messenger RNA stability which is
referred to as RNA interference (RNAi). This process can be mimicked by small synthetic
RNA, so called small inhibitory RNA (siRNA). In addition to the newly identified role of
RNA in gene-silencing, it is known that RNA is also a target for immune recognition
principles. Even more, siRNA can induce activation of some cell-types of the innate
immune system thus mediating off-target effects. Immune-recognition of RNA is
mediated by three members of the Toll-like-receptor family (TLR 3,7 and 8) as well as
by the cytosolic RNA-binding proteins RIG-I and MDA5. Additional, there are evidences
that RNA recognition occurs in a cell-type specific manner.
We aimed to identify RNA motives, which determine the immunostimulatory potential of
RNA and RNA oligonuclotides, such as siRNAs. We show that functional siRNAs were
immunostimulatory on several cell-types of the innate immune system. By introducing
uridine modifications, immunostimulation could be reduced significantly, whereas
modifications of other nucleotides showed only marginal effects. We further show that
bacterial RNA preparations were immunostimulatory not only on cells of the immune
system but also were able to stimulate normal tissue cells. We can also show that
recognition of bacterial RNA differs significantly from recognition of RNA
oligonucleotides.