Event date:
Nov 19 2021 4:00 pm

A Small RNA-Based Innate Immune System Guards the Integrity of Germ Cell Genomes

Professor Dr. Gregory Hannon
PIWI-family proteins and their associated small RNAs (piRNAs) act in an evolutionarily conserved innate immune mechanism that provides an essential protection for germ cell genomes against the activity of mobile genetic elements. piRNA populations comprise a molecular definition of transposons that permits them to be distinguished from host genes and selectively silenced. piRNAs can be generated in two distinct ways. Primary piRNAs emanate from discrete genomic loci, termed piRNA clusters, and appear to be derived from long, single-stranded precursors. The biogenesis of primary piRNAs involves at least two nucleolytic steps. Zucchini cleaves piRNA cluster transcripts to generate monophosphorylated piRNA 5’ ends. piRNA 3’ ends are likely formed by exonucleolytic trimming, after a piRNA precursor is loaded into its PIWI partner. Secondary piRNAs arise during the adaptive ping-pong cycle, with their 5’ termini being formed by the activity of PIWIs themselves. At least in Drosophila, piRNAs are maternally deposited and transmit an epigenetic signal essential for the effective control of at least some transposable elements. Our continuing efforts combine genetics, biochemistry, structural biology, and evolutionary and computational approaches to understand how the piRNA pathway effectively discriminates self from non-self at the genomic level.

Professor Dr. Gregory Hannon is our next guest in the zooming Molecular and Cellular Biology Colloquium Series which is a regular feature by the Department of Biology at SBASSE.

For those who are interested in life sciences, this is going to be an exciting talk.


About the speaker:

Greg Hannon FRS FMedSci is a professor of molecular cancer biology and director of the Cancer Research UK, Cambridge Research Institute at the University of Cambridge. Professor Hannon is internationally recognized for his contributions to small RNA biology, cancer biology, and mammalian genomics. He has a long history in the discovery of cancer genes, beginning with work at CSHL that led to the identification of CDK inhibitors and their links to cancer. More recently, his work has focused on small RNA biology, which led to an understanding of the biochemical mechanisms and biological functions of RNAi. Building upon this foundation, he has developed widely used tools and strategies for manipulation of gene expression in mammalian cells and animals and has generated genome-wide shRNA libraries that are available to the cancer community. He was among the first to uncover roles for microRNAs in cancer, including the discovery of the miR-17-92 cluster as an oncogene, the placement of miR-34 within the p53 pathways, and the understanding that let-7 and miR-93 are critical regulators of both normal stem cells and tumor initiating cells in several tissues. His laboratory also discovered the piRNA pathway and linked this to transposon repression and the protection of germ cell genomes. He has a continuous history of collaboration and technological innovation, including the development of selective re-sequencing strategies that are now being used within TCGA and the 1000 Genomes project.