Piwi-interacting (pi) RNAs are a recently discovered class of
small regulatory RNAs that interact with the Piwi subfamily
of Argonaute proteins. Piwi-piRNA complexes (piRCs) have been
implicated in transposon control and silencing, and are thought
to function through a mechanism in which the piRNA identifies and
binds the transposon transcript, which is subsequently cleaved
by Piwi. In addition, Piwi proteins have been implicated
in germline and stem cell self-renewal, and may be involved
in cancer cell proliferation. Given the importance of piRCs
in cellular maintenance and genome defense, insight into the
fundamental mechansims for their biogenesis and function will
be critical in our understanding of cancer biology. Currently,
the mechanism by which piRNAs are generated and the enzymes
involved in their initial processing are poorly understood.
The goal of my research is to identify unknown factors involved
in piRNA biogenesis, and to biochemically and structurally
characterize the piRNA processing machinery.