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Brenda Bass

Professor of Biochemistry

B.A. Colorado College

Ph.D. University of Colorado, Boulder

Research

References

 

Brenda Bass's Lab Page

Brenda Bass' PubMed Literature Search

Research

Research in my laboratory is focused on double-stranded RNA (dsRNA)--its biologic functions and the proteins that bind it to mediate these functions. Our studies are divided between two dsRNA-mediated pathways: RNA editing by adenosine deaminases that act on RNA (ADARs), and gene-silencing (e.g., RNA interference). For both pathways we perform in vitro studies to answer mechanistic questions, and in vivo studies in C. elegans to understand biologic function. dsRNA binding proteins (dsRBPs) bind tightly to dsRNA of any sequence, and a dsRNA substrate for one dsRBP is also a substrate for others. Thus, dsRNA-mediated pathways intersect, and we also study how RNA editing affects dsRNA-mediated processes such as gene-silencing.

ADARs deaminate adenosines in double-stranded regions of cellular and viral RNAs to create the nucleoside inosine. Inosine is read as guanosine by the ribosome, and one function of ADARs is to deaminate adenosines within codons. Editing in codons creates multiple protein isoforms from a single, encoded mRNA, and is particularly important for proteins involved in neurotransmission (e.g., serotonin and glutamate receptors). Several years ago my laboratory made the surprising discovery that the predominant site of editing by ADARs is not in codons, but in long double-stranded structures found in non-coding regions of mRNAs (UTRs and introns). We are attempting to understand the function of these double-stranded structures and the inosines within them, and in particular, their possible role in regulating translation. Finally, we are also using biochemical techniques to explore questions about ADAR catalysis and substrate specificity, and here we are assisted by the x-ray crystal structure of human ADAR2 that we solved in collaboration with Dr. Chris Hill (University of Utah).

An exciting discovery of the last decade is the numerous small RNAs that derive from dsRNA encoded within an organism’s genome (e.g., miRNA and siRNA). We are interested in characterizing the dsRNA precursors of these small RNAs, whether they are edited by ADARs, and how they are processed by Dicer. In regard to Dicer, we are trying to understand how Dicer’s helicase domain contributes to processing of dsRNA to produce siRNA. We are using in vitro biochemical methods to test our hypothesis that the helicase domain allows the enzyme to translocate along dsRNA in a processive manner. We are also using C. elegans strains expressing either wildtype Dicer, or Dicer with mutations in its helicase domain, to understand the in vivo role of the helicase domain. Using deep-sequencing and bioinformatics methods we determined that the helicase domain is essential for the production of certain endogenous siRNA. Future studies will be aimed at determining why these small RNAs require Dicer’s helicase domain.

References