[IIGB_All] TODAY: IIGB Seminar, Megan Norris

[Aaliyah Kelley]

[cid:26f8a9ce-45dd-4071-bf14-abfc7727c3d6]


 You are cordially invited to attend

     Megan Norris

      University of California Riverside

[cid:586ba137-2fcd-42f3-857f-28f34b353d62]

Role and regulation of mRNA localization to cell protrusions in migrating cells

        Date: Friday, November 22

     Time: 12pm - 1:00 pm

      Location: Genomics Auditorium 1102


Abstract: Subcellular localization of RNAs is a post-transcriptional process that tunes protein output in space and time. Mis-regulation of RNA localization has been linked to defects in development and is negatively correlated with cancer prognosis. Despite evidence of biological importance, the particular localized RNAs, mechanistic effect on cell behavior and importance to the embryo and disease state remain unknown. A critical barrier has been the lack of an experimental system that allows both mechanistic- and organismal-level analyses, which is further compounded by the difficulty of prioritizing candidates from multiple hundred localized RNAs. To address this, I developed a pipeline for discovery and prioritization of RNA localization candidates. The pipeline uses RNA-seq on fractionated cells, comparative analyses, rapid phenotypic screening and cursory identification of cis-elements to identify RNA candidates that are both tractable and biologically interesting. By applying the pipeline to mouse melanoma cells, I found that mRNA for the kinesin motor protein Kif1c must be localized to cell protrusions for proper cell migration. I identified a short, GA-rich element in the Kif1c 3’UTR that is required for mRNA localization. Loss of the GA-element inhibits Kif1c mRNA enrichment but has no effect on total Kif1c mRNA abundance. Changes in mRNA localization also do not affect localization of the encoded KIF1C protein. Instead, protein encoded by the mis-localized mRNA loses binding partner specificity. Surprisingly, only some, but not all, functions of KIF1C were sensitive to Kif1c mRNA localization. Thus, mRNA localization to cell protrusions helps establish distinct functional pools of KIF1C protein. This work demonstrates a novel functionality for the spatial regulation of gene expression in migrating cells.


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