Messenger RNA localization plays a key role in creating the asymmetric distributions of proteins necessary for cellular and developmental polarity. Impairment of mRNA localization pathways has been implicated in human diseases such as spinal muscular atrophy and fragile X syndrome and targeting of mRNAs to cancer cell protrusions suggests a role in metastasis. The sorting of specific mRNAs to different subcellular domains is a complex process involving the assembly and trafficking of ribonucleoprotein particles (RNPs). How specificity is conferred on this process, particularly in cells where many mRNAs are localized concurrently, is poorly understood. This proposal integrates biochemical, genetic, and quantitative and live imaging-based approaches to investigate how different mRNAs are specifically recognized to form localization competent RNPs and assembled into higher order, functional RNA granules.
Aims 1 and 2 address the end masse localization of numerous transcripts to the germ plasm at the posterior of the Drosophila oocyte and their differential inheritance by germ cell progenitors. This system affords an ideal opportunity to investigate the molecular mechanisms that regulate the formation, composition, and behavior of RNPs essential for localization and function in generating asymmetry.
Aim 3 capitalizes on our recent identification of a large number of localized RNAs in Drosophila sensory neuron dendrites. The major goals of this aim are to critically assess the functional significance of RNA localization in neurons and to probe the generality of the mechanistic principles emerging from Aims 1 and 2.
Messenger RNA localization is a widely used mechanism for producing proteins in particular regions of cells where their functions are needed and plays a well-documented role in animal development and in the formation and function of polarized cells like neurons. Impairment of mRNA localization pathways has been implicated in human diseases such as spinal muscular atrophy and fragile X syndrome and localization of mRNAs to cancer cell protrusions may be important in metastasis. The proposed studies will shed light on the mechanisms used to direct mRNAs to their specific destinations and how the disruption of this process may lead to diseases like cancer or neurological dysfunction.
|Niepielko, Matthew G; Eagle, Whitby V I; Gavis, Elizabeth R (2018) Stochastic Seeding Coupled with mRNA Self-Recruitment Generates Heterogeneous Drosophila Germ Granules. Curr Biol 28:1872-1881.e3|
|Eagle, Whitby V I; Yeboah-Kordieh, Daniel K; Niepielko, Matthew G et al. (2018) Distinct cis-acting elements mediate targeting and clustering of Drosophila polar granule mRNAs. Development 145:|
|Lerit, Dorothy A; Shebelut, Conrad W; Lawlor, Kristen J et al. (2017) Germ Cell-less Promotes Centrosome Segregation to Induce Germ Cell Formation. Cell Rep 18:831-839|
|Tenenbaum, Conrad M; Misra, Mala; Alizzi, Rebecca A et al. (2017) Enclosure of Dendrites by Epidermal Cells Restricts Branching and Permits Coordinated Development of Spatially Overlapping Sensory Neurons. Cell Rep 20:3043-3056|
|Abbaszadeh, Evan K; Gavis, Elizabeth R (2016) Fixed and live visualization of RNAs in Drosophila oocytes and embryos. Methods 98:34-41|
|Trovisco, Vítor; Belaya, Katsiaryna; Nashchekin, Dmitry et al. (2016) bicoid mRNA localises to the Drosophila oocyte anterior by random Dynein-mediated transport and anchoring. Elife 5:|
|Misra, Mala; Edmund, Hendia; Ennis, Darragh et al. (2016) A Genome-Wide Screen for Dendritically Localized RNAs Identifies Genes Required for Dendrite Morphogenesis. G3 (Bethesda) 6:2397-405|
|Tenenbaum, Conrad M; Gavis, Elizabeth R (2016) Removal of Drosophila Muscle Tissue from Larval Fillets for Immunofluorescence Analysis of Sensory Neurons and Epidermal Cells. J Vis Exp :|
|Little, Shawn C; Sinsimer, Kristina S; Lee, Jack J et al. (2015) Independent and coordinate trafficking of single Drosophila germ plasm mRNAs. Nat Cell Biol 17:558-68|
|López-Panadès, Elisenda; Gavis, Elizabeth R; Casacuberta, Elena (2015) Specific Localization of the Drosophila Telomere Transposon Proteins and RNAs, Give Insight in Their Behavior, Control and Telomere Biology in This Organism. PLoS One 10:e0128573|
Showing the most recent 10 out of 25 publications