Topic: Using oocytes to reveal the molecular function and mechanism of action of FMRP
Speaker: Assistant Professor Ethan Greenblatt, Department of Biochemistry and Molecular Biology, the University of British Columbia (UBC)
Date and time: April 22, 10:15–11:45
Venue: Auditorium, L Building
Host: Wang Chenhui
Abstract:
Defects in oocyte function are thought to contribute substantially to the high rate of miscarriage estimated at 30–70%. Human oocytes are uniquely dependent on ongoing translation using long-lived ribosomes and mRNAs since meiotic maturation occurs following a period of transcriptional quiescence lasting for at least several weeks. To understand the impact of oocyte storage/aging on meiotic competence, we developed a Drosophila model of oocyte aging. The meiotic spindles of Drosophila oocytes became disorganized with prolonged storage, resembling transient tripolar or unipolar spindles frequently observed in human and aged mouse oocytes. Emerging genetic and biochemical analyses from our lab implicate the aging of the cytoplasm, and in particular of ribosomes, as a key driver of oocyte meiotic spindle instability. We also study the role of RNA binding proteins which promote selective translation in oocytes. These factors are essential not only for oocyte survival, but also support selective translation in the nervous system and are mutated in human neurological disorders. We find that proteins such as FMRP, UBAP2L, and G3BP form physical complexes along mRNAs and are essential for ongoing translation from subsets of oocyte transcripts. Our data support a model in which these factors recognize specific features of cellular mRNAs, such as long coding regions, in order to maintain basal levels of gene expression of essential factors within an otherwise highly translationally repressive environment.
Biography:
2021–current, Assistant Professor, University of British Columbia
2012–2020, Postdoctoral Fellow, Carnegie Institute for Science, Baltimore, MD
2007–2011, PhD in Biophysics, Stanford University
2005–2007, Graduate student, Department of Chemistry, Stanford University