Tuesday, May 15, 2012
General Biology Seminar
What fruit flies teach us about RNA silencing
Phillip Zamore, Prof. of Biomedical Sciences, University of Mass.
RNA silencing is remarkably similar between fruit flies and man. Like humans, flies have three distinct RNA-guided mechanisms to silence genes: the microRNA (miRNA), the siRNA-guided RNA interference (RNAi), and Piwi-interacting RNA (piRNA) pathways (1). These three classes of small RNAs are produced by different pathways from different types of precursor RNAs, but each functions as a sequence-specific guide for a member of the Argonaute family of proteins (2). Much of what we know about these three types of small silencing RNAs was learned through biochemical and genetic studies in the model organism, Drosophila melanogaster (3-5). For each pathway, the fundamental mechanisms for small RNA biogenesis and function were discovered first in flies, then in man. In flies, each pathway serves a unique and largely non-overlapping function. We know that miRNAs regulate the expression of protein coding genes, RNAi defends against viral infection and transposons in the soma, and piRNAs protect the germ line from selfish genetic elements such as transposons. New functions for small silencing RNAs continue to be discovered. What are the lessons taught us by flies and how can we apply them to develop robust RNAi strategies for drug-target discovery and human therapy? Finally, what discoveries in flies remain to be translated into improvements in triggering RNA silencing in mammals?