piRNA Biogenesis and Function in Germline Development

Univ Of Massachusetts Med Sch Worcester, Worcester MA

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Abstract

DESCRIPTION (provided by applicant): The piRNA pathway has a conserved role in transposon silencing and genome maintenance during germline development. Adaptation to new genome pathogens by the Drosophila piRNA genome defense system appears to be driven by transposition into heterochromatic clusters, which produce the primary piRNAs that to initiate silencing. The HP1 homolog Rhino binds to clusters and is evolving rapidly under positive selection, suggesting that it may co-evolve with invading mobile elements. piRNA clusters and Rhino thus function at the adaptive interface between the piRNA pathway and transposons. Aims1 and 2 combine evolutionary divergence and conservation with genetic, genomic, computational and cytological tools to define this critical interface. The ability to differentiate cluster transcripts from mRNAs is critical to the specificity of the piRNA dense system, and our recent data suggest that stalled spicing may mark cluster transcripts for processing into silencing RNAs. Aim 3 focuses on the role of splicing in piRNA precursor sorting into the silencing pathway. These studies address mechanisms that maintain the inherited genome and are likely to directly impact reproductive health.