The primary goal of this application is to understand how the RNA editing enzymes called Adenosine Deaminases that act on RNA (ADARs) function in the nervous system. Caenorhabditis elegans will be used for these studies, and strains lacking all ADARs have been isolated and found to exhibit behavioral defects. To correlate expression of ADARs in particular neurons with particular behaviors, ADARs will be expressed in specific neurons of mutant strains, and phenotypic rescue monitored. Other studies will focus on determining the relevant edited RNAs. Microarray analyses and inosine-specific cleavage strategies are proposed. These methods will identify inosines in coding as well as non-coding regions of mRNAs, but the latter will be the focus of further study. Experiments to determine how mRNAs with inosines in non-coding sequences are metabolized in vivo, and how this metabolism changes in the absence of RNA editing will be performed. Recent experiments indicate ADARs intersect with RNA interference pathways, and possible mechanisms for this will be tested. Understanding the molecular determinants of behavior is one of the last frontiers of molecular biology. This application offers the potential for new discoveries in behavior, gene silencing and the general roles of dsRNA in cells.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZRG1-SSS-U (04))
Program Officer
Bender, Michael T
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University of Utah
Schools of Medicine
Salt Lake City
United States
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Reich, Daniel P; Tyc, Katarzyna M; Bass, Brenda L (2018) C. elegans ADARs antagonize silencing of cellular dsRNAs by the antiviral RNAi pathway. Genes Dev 32:271-282
Blango, Matthew G; Bass, Brenda L (2016) Identification of the long, edited dsRNAome of LPS-stimulated immune cells. Genome Res 26:852-62
Whipple, Joseph M; Youssef, Osama A; Aruscavage, P Joseph et al. (2015) Genome-wide profiling of the C. elegans dsRNAome. RNA 21:786-800
Kuttan, Ashani; Bass, Brenda L (2012) Mechanistic insights into editing-site specificity of ADARs. Proc Natl Acad Sci U S A 109:E3295-304
Warf, M Bryan; Shepherd, Brent A; Johnson, W Evan et al. (2012) Effects of ADARs on small RNA processing pathways in C. elegans. Genome Res 22:1488-98
Bass, Brenda; Hundley, Heather; Li, Jin Billy et al. (2012) The difficult calls in RNA editing. Interviewed by H Craig Mak. Nat Biotechnol 30:1207-9
Eggington, Julie M; Greene, Tom; Bass, Brenda L (2011) Predicting sites of ADAR editing in double-stranded RNA. Nat Commun 2:319
Warf, M Bryan; Johnson, W Evan; Bass, Brenda L (2011) Improved annotation of C. elegans microRNAs by deep sequencing reveals structures associated with processing by Drosha and Dicer. RNA 17:563-77
Evan Johnson, W; Welker, Noah C; Bass, Brenda L (2011) Dynamic linear model for the identification of miRNAs in next-generation sequencing data. Biometrics 67:1206-14
Hundley, Heather A; Bass, Brenda L (2010) ADAR editing in double-stranded UTRs and other noncoding RNA sequences. Trends Biochem Sci 35:377-83

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