KEYNOTE SPEAKER 5: March 26, 2021, 11:05–12:00 pm
Blog by MiSciWriters
“Distinguishing self and non-self dsRNA in vertebrates and invertebrates”
Brenda Bass, Ph.D.
Distinguished Professor of Biochemistry
University of Utah
When a virus infects an animal cell, including a human cell, double-stranded RNA (dsRNA) matching the viral sequence is found in the cell. Viral dsRNA is recognized as foreign and an immune response is mounted. Recently it has been realized that animal cells encode and synthesize their own dsRNA. My laboratory is interested in the poorly understood functions of cellular dsRNA, and further, how cells distinguish the good cellular dsRNA (self) from the bad viral dsRNA (non-self). ADAR RNA editing enzymes and RIG-I-like receptors play key roles in distinguishing self and non-self dsRNA in both vertebrates and invertebrates, and we are interested in how these pathways diverged. While vertebrates use an interferon pathway to mount an antiviral response, invertebrates lack this pathway, and instead, use RNA interference (RNAi) in antiviral defense. The enzyme Dicer is key to the antiviral RNAi pathway and is essential for cleaving viral dsRNA during the invertebrate immune response. Our prior cryo-EM and biochemistry analyses indicate Dicer’s helicase domain recognizes the ends of viral dsRNA as “non-self”, or foreign, engaging the dsRNA in a process that involves unwinding, clamping around the dsRNA, and threading the dsRNA to the RNase III cleavage sites. We are currently using transient kinetics to understand the role of ATP in coordinating the catalytic steps of this fascinating molecular machine.
Sinha NK, Iwasa J, Shen PS, Bass BL. Dicer uses distinct modules for recognizing dsRNA termini. Science (New York, NY). American Association for the Advancement of Science; 2018 Jan 19;359(6373):329–334. PMCID: PMC6154394
Raushan K. Singh, McKenzie Jonely,