Research

Small RNA pathways protect the genome against foreign RNAs, such as viruses, in addition to regulating many endogenous RNAs, including aberrant transcripts, pseudogenes, and non-coding regions. The Phillips lab uses genetics, cell biology, and biochemistry to understand how RNA silencing pathways modulate gene expression and maintain genome integrity. Small RNAs are generally ~20-30 nucleotides in length and associate with an Argonaute protein. There are three major classes of small RNAs – microRNAs (miRNAs), small-interfering RNAs (siRNAs), and Piwi-interacting RNAs (piRNAs), which are defined by their mode of biogenesis, protein cofactors, and mechanism of action. We and others have identified a group of genes (the mutator class) that are required for RNA interference (RNAi), transposon silencing, and production of endogenous siRNAs (endo-siRNAs) in the nematode, C. elegans. The mutator genes act downstream of primary siRNAs (produced by the endoribonuclease, Dicer) and piRNAs, and are required for the production of 22-nt “secondary” siRNAs. Our research will have important implications in the understanding of how RNA silencing pathways inhibit transposon movement and repress aberrant RNAs to prevent deleterious gene mutations that can result in infertility, birth defects, as well cancer and other diseases.

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