Brenda Bass

When a virus infects an animal cell, including human cells, 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. During the past decade it has been realized that animal cells encode and synthesize their own dsRNA. Studies in the Bass lab are focused on dsRNA--its biological functions and the proteins that bind it to mediate these functions. We are also interested in how cells distinguish the good from the bad— the cellular dsRNA (self) from the viral dsRNA (non-self). To facilitate our studies, we performed genome-wide analyses to map long dsRNA expressed in C. elegans, mouse, and human. These "dsRNAomes" show that long dsRNA is predominantly encoded in protein coding genes, in introns or 3' UTRs.

In vertebrates, viral dsRNA is recognized by RIG-I-like receptors (RLRs) to trigger an interferon response, while in invertebrates, Dicer cleaves viral dsRNA to generate siRNAs that silence viral transcripts. RLRs and Dicer all contain a conserved helicase domain, suggesting this domain functioned in antiviral defense in a common ancestor. Our comparative studies of invertebrate and vertebrate Dicers reveal interesting differences, likely reflecting divergence of innate immune pathways.

Current goals:

• To use Ancestral Protein Reconstruction to understand how innate immune pathways evolved in animals.
• To determine dsRNAomes for diverse animals to reveal paradigms and increase our understanding of the biological functions of dsRNA binding proteins, such as ADARs and Dicer.
• To understand the mechanism of the C. elegans antiviral complex using biochemistry and structural biology (cryo-EM).
• To understand, in diverse animals, how the RLR family of helicases distinguish self dsRNA from non-self viral dsRNA and how RNA editing enzymes affect this discrimination.
• To resurrect human Dicer so it can function in antiviral defense in humans.