489B Poster - 06. Regulation of gene expression
Friday April 08, 2:00 PM - 4:00 PM

Authors:
KAICHENG MA; Al Rohet Hossain; Kayla Judson; Ethan Greenblatt

Affiliation: The University of British Columbia

Keywords:
h. translational regulation; j. RNA binding proteins

Fmr1 encodes an RNA binding protein FMRP necessary for proper ovary and neuronal development. Mutations in Fmr1 lead to fragile X syndrome, the most commonly inherited intellectual disability (ID) autism-associated disorder. By studying Fmr1's role in transcriptionally silent mature Drosophila oocytes, we recently discovered that Fmr1 functions primarily to promote the translation initiation of genes encoding large proteins, many of which are orthologs of human genes associated with ID and autism.

In order to identify FMRP binding partners and elucidate the mechanism of Fmr1-dependent translation, we used CRISPR to tag Fmr1 at its endogenous locus and performed IP-mass spectrometry experiments from ovarian extracts. We also determined which FMRP binding partners are required for its activity by using a novel single molecule fluorescence in situ hybridization (smFISH)-based assay, in order to assess Fmr1’s activity in the absence of its binding partners.

Our preliminary data identify a critical role for the RNA and ubiquitin binding protein lingerer (lig). We find that lig physically associates with FMRP, and the loss of lig appears to strongly diminishes FMRP's activity towards one of its targets. Previous studies of the mammalian lig ortholog UBAP2L in cultured cells have shown that it can bind to ribosomes to promote translation. In flies, lig is required for proper copulation behavior and short-term memory. Our data indicate that lig acts in vivo with FMRP to promote the production of FMRP targets, a function which is likely to be critical for proper neuronal and ovarian function.