Cellular double-stranded RNAs and aberrant immune response: From identification to application in human disease

Attendees must use Discount code GTWEB2020 to attend this webinar for free.

Protein Kinase RNA-activated (PKR) is a ubiquitously expressed enzyme well known for its role during immune response. Upon binding to viral double-stranded RNAs (dsRNAs), PKR undergoes dimerization and autophosphorylation. Activated/Phosphorylated PKR (pPKR) then regulates translation and provides cue to multiple signaling pathways. Recently, growing evidence suggests that PKR can be phosphorylated even in uninfected cells by endogenously expressed cellular dsRNAs.

Our laboratory investigates regulation and function of cellular dsRNAs through their interaction with innate immune response proteins such as PKR. To elucidate the identity of cellular dsRNAs, we employed formaldehyde mediate crosslinking-immunoprecipitation sequencing and captured PKR-interacting RNAs during the mammalian cell cycle. Our analyses reveal that PKR binds to diverse types of noncoding RNAs from the nuclear gene. Interestingly, a major class of PKR-interacting RNAs is provided by mitochondrial RNAs. Mitochondrial RNAs can form intermolecular dsRNAs owing to bidirectional transcription of the circular mitochondrial genome and regulate PKR phosphorylation and signaling. In this presentation, we discuss our recent efforts to identify cellular dsRNAs and investigate their function with respect to human disease.