Talk abstracts
Talk on Thursday 11:35-11:55am submitted by Agnes Karasik
The role of RNA cleavage in innate immunity
Agnes Karasik (Department of Chemistry and Biochemistry)
Abstract:
My laboratory is broadly interested in investigating RNase function related to human health and disease. In the last few years (as a postdoctoral fellow), I became interested in studying RNA cleavage by RNase L, a key player of the innate immune response. Active RNase L cleaves most single stranded RNAs, leading to widespread RNA decay in the cytoplasm. This in turn induces the inflammatory response and ultimately triggers cell death. However, the molecular connection between these outcomes and RNA cleavage was unknown. I found that activation of RNase L leads to the accumulation of mRNA fragments in the cell that are still being translated. Since some of these RNA fragments dont have a stop codon, ribosomes stall and collide at their 3 end. Subsequently, this triggers the activation of a ribosome collision sensor, ZAK&alpha and downstream signaling via the p38 and JNK kinases. This induces the inflammatory response and ultimately causes cell death. Thus, my work revealed the molecular mechanism on how a non-specific endonuclease can induce physiological changes in the cell during the innate immune response.
Keywords: RNA cleavage, translation, Ribotoxic Stress Response