Gene and genome regulation by RNAi and small RNAs. Molecular biology of germline gene and transposon
Lau, Nelson C.
Small regulatory RNAs (and their associated proteins) are dynamic and active participants in controlling the genome and phenotype of cells and animals. Germ cells have a special role in the perpetuation of organisms, but they have also become the richest environment for the study of small regulatory RNAs. In addition to microRNAs, which are vital regulators conserved from plants to people, germ cells express endogenous small interfering RNAs (endo-siRNAs) and Piwi-interacting RNAs (piRNAs). In animal germ cells, like spermatocytes and oocytes, piRNAs are the most abundant class of small RNAs, and together with Piwi proteins, they suppress the mobilization of transposable elements and specify the organization of mRNAs and proteins in the germ cell, which impacts the expression of certain genes
Our group is interested in dissecting the molecular mechanisms of Piwi proteins and piRNAs, with a focus on particular outstanding questions. How exactly do Piwi proteins and piRNAs silence transposons and organize asymmetrically in germ cells? What is the impact of these molecules on global gene expression and chromatin organization and how does this affect germ cell and embryonic development? How do piRNAs get generated and what triggers their specific expression in germ cells? We hope to address these questions with molecular, cell biology, and biochemical approaches in specific model systems, like Xenopus oocytes, a repository and "living test tube" of Piwi proteins and piRNAs. Insights we gain from piRNA studies will complement our examinations of other RNAi pathways, like microRNAs and endo-siRNAs.