This year over 350 Bay Area RNA researchers convened on the UCSF campus to mingle and schmooze, have a coffee, and discuss all things related to RNA. The meeting comprised 20 graduate student and postdoc talks and more than 50 posters. Out of these excellent presentations Maxine Umeh (Cleary Lab, UC Merced) and Phillip Dumesic (Madhani Lab, UCSF) won awards.
Best Talk Award- Maxine Umeh (graduate student, Cleary Lab)
Maxine is a third year graduate student in Michael Cleary’s lab at UC Merced. She grew up in Sacramento and moved to Merced in 2007 to pursue a BS in Developmental Biology where she became interested in studying nervous system development. She is currently using whole genome microarray analysis to construct mRNA decay regulatory networks in the Drosophila embryonic nervous system using a novel technique known as TU-Tagging. Her abstract is below.
Identification of mRNA decay networks in the Drosophila nervous system. Models of gene expression during development traditionally focus on the regulation of mRNA transcription. However, an essential level of control occurs via mRNA decay. mRNA decay is likely to be important during nervous system development, where the structure of neurons requires localized translation of mRNAs far from their site of synthesis and the generation of cellular diversity requires rapid turnover of mRNAs that regulate proliferation and differentiation. The study of mRNA decay during embryonic development has previously been hindered by the lack of methods allowing in vivo, cell type-specific measurements of transcript stability. We have developed a technique, called TU-decay, that overcomes this technical challenge and allows neural-specific, genome-wide measurements of mRNA decay in intact Drosophila embryos. This technique provides the foundation for a systems-level approach that we are using to construct a neural development mRNA decay network. Our comparisons of whole embryo and neural-specific mRNA half-lives have identified mRNAs that are selectively stabilized or destabilized in the nervous system. TU-decay analysis has also revealed transcript decay kinetics that correlate with the function of the encoded protein. For example, mRNAs that are known to be translated within axon growth cones or dendrites have long half-lives while mRNAs encoding signaling proteins and transcription factors that regulate cell fate decisions have short half-lives. We used multiple computational approaches to identify candidate cis-regulatory elements that determine mRNA stability, including sequences recognized by the RNA-binding protein Pumilio, AU-rich element binding proteins, and micro-RNAs. Our long-term goal is to generate a comprehensive and predictive network map of neural mRNA decay dynamics, thus filling a significant gap in current models of gene expression during neural development.
Best Poster Award- Phillip Dumesic (postdoc, Madhani Lab)
Phillip is a fourth year graduate student in the MD-PhD program at the University of California, San Francisco. He received a BS from Stanford University, where he studied skin development and tumorigenesis in the lab of Paul Khavari. At UCSF, he is advised by Hiten Madhani and investigates mechanisms by which organisms distinguish their own genetic material from that of foreign elements. His abstract is below.
Stalled spliceosomes are a signal for RNAi-mediated genome defense. Using the yeast Cryptococcus neoformans, we describe a mechanism by which transposons are initially targeted for RNAi-mediated genome defense. We show that intron-containing mRNA precursors template siRNA synthesis. We identify a Spliceosome-Coupled And Nuclear RNAi (SCANR) complex required for siRNA synthesis and demonstrate that it physically associates with the spliceosome. We find that RNAi target transcripts are distinguished by suboptimal introns and abnormally high occupancy on spliceosomes. Functional investigations demonstrate that the stalling of mRNA precursors on spliceosomes is required for siRNA accumulation. Lariat debranching enzyme is also necessary for siRNA production, suggesting a requirement for processing of stalled splicing intermediates. We propose that recognition of mRNA precursors by the SCANR complex is in kinetic competition with splicing, thereby promoting siRNA production from transposon transcripts stalled on spliceosomes. Disparity in the strength of expression signals encoded by transposons versus host genes offers an avenue for the evolution of genome defense.Continue reading...