(Project Leader: Noelle L'etoile) Addiction, learning deficits and cognitive decline are all mounting public health concerns. Each pathology results in a large part from aberrant neuronal plasticity. Thus, understanding the cellular and molecular basis for neuronal plasticity is of great interest. The role of extracellular RNA in neuronal plasticity has just been uncovered by our lab's unpublished work. We propose to use the powerful cell biological and genetic model organism C. elegans to discover pathways that produce and utilize exRNA and develop tools to visualize, with sub-cellular resolution, exRNAs in vivo. Mounting biochemical evidence has accumulated for exRNAs in mammals. In C. elegans the phenomenon of RNAi spreading, which requires exRNAs, is well documented. However, it is still unclear how exRNAs are produced, secreted, trafficked from one tissue type to the next, or how they alter target tissue biology. These gaps result from a paucity of tools providing high resolution, high sensitivity imaging of small RNAs in an intact organism and the lack of genetic screens for pathways required for the production and function of environmentally induced exRNAs. We have evidence that C. e/egans sensory neurons produce small RNAs in response to environmental stimulation. Though these small RNAs arise from the sensory neuron, we find they induce organism-wide increases in small RNA. This increase is dependent upon the double stranded RNA channel, SID-1. We used this observation to develop exRNA reporter strains. These will be used in screens for genes required for biogenesis, secretion, trafficking and utilization of stimulus-induced exRNAs. The stimulus forexRNA production comes from either the environment in the form of odors or from within the cell in the form of oncogene activation. This study will provide detailed genetic and cell biological insight into how endogenously triggered 22G RNAs and medically relevant microRNAs are produced and act at a distance from their source cell to affect organismal biology. The genes we identify and the imaging tools we develop in this project may provide novel mechanistic insight into the medically relevant roles of exRNA..And the irhaging tools could revolutionize small RNA cell biology by providing quantitative images of small RNAs at subcellular resolution.

Public Health Relevance

Neuronal plasticity underiies both normal learning and pathological addictions. As such, understanding the cellular and molecular basis for adaptation is critical.for human health. Our recent findings have implications for a new mode of transmission of environmentally induced behavioral changes as epigenetic changes in genes that control behavior from one generation to the next.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZRG1-OBT-S (50))
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University of California San Francisco
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Montoya, Misty M; Ansel, K Mark (2017) Small RNA Transfection in Primary Human Th17 Cells by Next Generation Electroporation. J Vis Exp :
Montoya, Misty M; Maul, Julia; Singh, Priti B et al. (2017) A Distinct Inhibitory Function for miR-18a in Th17 Cell Differentiation. J Immunol 199:559-569
Singh, Priti B; Pua, Heather H; Happ, Hannah C et al. (2017) MicroRNA regulation of type 2 innate lymphoid cell homeostasis and function in allergic inflammation. J Exp Med 214:3627-3643
Ong, Wei Qiang; Citron, Y Rose; Sekine, Sayaka et al. (2017) Live Cell Imaging of Endogenous mRNA Using RNA-Based Fluorescence ""Turn-On"" Probe. ACS Chem Biol 12:200-205
Anderton, Brittany; Camarda, Roman; Balakrishnan, Sanjeev et al. (2017) MYC-driven inhibition of the glutamate-cysteine ligase promotes glutathione depletion in liver cancer. EMBO Rep 18:569-585
Chen, Baohui; Hu, Jeffrey; Almeida, Ricardo et al. (2016) Expanding the CRISPR imaging toolset with Staphylococcus aureus Cas9 for simultaneous imaging of multiple genomic loci. Nucleic Acids Res 44:e75
Cheung, Kei-Hoi; Keerthikumar, Shivakumar; Roncaglia, Paola et al. (2016) Extending gene ontology in the context of extracellular RNA and vesicle communication. J Biomed Semantics 7:19
Ong, Wei Qiang; Citron, Y Rose; Schnitzbauer, Joerg et al. (2015) Heavy water: a simple solution to increasing the brightness of fluorescent proteins in super-resolution imaging. Chem Commun (Camb) 51:13451-3
Li, Kang; Ching, Daniel; Luk, Fu Sang et al. (2015) Apolipoprotein E enhances microRNA-146a in monocytes and macrophages to suppress nuclear factor-?B-driven inflammation and atherosclerosis. Circ Res 117:e1-e11
Pua, Heather H; Ansel, K Mark (2015) MicroRNA regulation of allergic inflammation and asthma. Curr Opin Immunol 36:101-8

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