CAREER: Arabidopsis Argonaute10-protein Interactome

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Intellectual Merit: Argonaute (AGO) proteins are key effectors of RNA-mediated gene silencing and act by binding to miRNAs to repress the expression of target genes at transcriptional or posttranscriptional levels. Whereas AGOs were previously thought to exclusively repress miRNA target genes, the PI's group recently discovered that Arabidopsis AGO10 specifically sequesters a single miRNA class, miR166 to positively regulate their targets. The mechanism of this regulation is unclear, but it may involve proteins that interact with AGO10. Preliminary studies identified several novel cofactors of AGO10, including two serine and arginine enriched splicing factors(SRSFs) and an AGO10-Interacting exoribonuclease (AGIER1), among others. These new findings interconnect RNA silencing with many previously unappreciated biological events such as mRNA splicing and AGO-channeled miRNA decay. To investigate these novel modes of AGO10 regulation, two specific objectives will be pursued: 1) Investigate the biochemical interaction between AGO10 and the SRSFs and its biological consequences; 2) Investigate how AGIER1 affects AGO10-miR166 function. Results will establish how AGO10/miR166 function is modulated and will reveal new layers of complexity in gene regulatory networks through miRNA function. Broader Impacts: The research provides unique and advanced training opportunities for undergraduates, and graduate students in broad areas. Research and educational objectives are integrated in this CAREER proposal through two strategies: 1) to recruit and train female and minority undergraduates for graduate studies in biochemical and genetic areas; and 2) to modernize and improve the quality of graduate training in RNA biology in classroom and research settings. These efforts will contribute to providing a creative and highly skilled workforce to support the U.S. economy.