EAGER: Small RNAs as hormones

EAGER：小 RNA 作为激素

• 批准号: 1230141
• 负责人: Noelle L'Etoile
• 金额: $ 25万
• 依托单位: University of California-San Francisco
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1230141&HistoricalAwards=false
• 关键词: EAGER; Small; RNAs; hormones

The central question that will be investigated in this project is whether a small RNA produced by one cell can influence gene expression in a different cell. Recently, small RNAs have been described that have the potential to specifically turn off their own genes. To date, this gene-silencing activity has only been observed within the cell that produces the RNA. The Principal Investigator proposes the very novel idea that small RNAs produced in odor-adapted neurons may act as hormones to elicit responses in the gonads. The expectation is that odor sensory neurons will adapt to odors by producing small RNAs that shut down neuron genes that respond to odors and, subsequently, these small RNAs will be released from neuronal cells and traffic to the gonad where they will induce changes that preempt expression of specific genes. The transparent nematode C. elegans with its powerful cell biology and genetics will serve as the model for these studies. Genetic disruption of small RNA secretion and signaling will be carried out to determine the effect of these small RNAs on tissues distant from the site of their production. The finding of such high content messengers would impact all aspects of biology as it would reveal for the first time that RNA can act as a hormone, and with such a capacity, could provide unprecedented specificity to the process of wide-spread down regulation of genes. The broader impacts of this work will involve training high school and Masters students, including students from underpriveleged families, in state of the art research. Specifically, students will be trained in a one-on one setting to design, execute, document and ultimately publish their work. This highly innovative and original research has great potential to add another dimension to our understanding of cell-cell communication networks that influence gene regulation in multicellular organisms.

该项目将研究的主要问题是，一个细胞产生的小RNA是否会影响不同细胞中的基因表达。 最近，已经描述了小型RNA，这些RNA有可能专门关闭自己的基因。 迄今为止，仅在产生RNA的细胞中观察到这种基因沉淀活性。 主要研究者提出了一个非常新颖的想法，即适应气味的神经元中产生的小RNA可能是引起性腺反应的激素。期望是气味感觉神经元通过产生小的RNA来适应气味，从而关闭对气味反应的神经元基因，随后，这些小的RNA将从神经元细胞中释放出来，并流量到性腺传播到性腺，在那里它们会诱导预发特定基因表达的变化。具有强大细胞生物学和遗传学的透明线虫秀丽隐杆线虫将作为这些研究的模型。 将进行小RNA分泌和信号传导的遗传破坏，以确定这些小RNA对远离生产部位的组织的影响。 这种高素质的使者的发现将影响生物学的各个方面，因为它首次揭示了RNA可以充当激素，并且具有这样的能力，可以为广泛抑制基因调节的过程提供前所未有的特异性。这项工作的更广泛的影响将涉及培训高中和硕士学生，包括来自弱势家庭的学生，在最先进的研究中。 具体来说，学生将在一对一的设置中接受培训，以设计，执行，文档并最终发布其作品。这项高度创新和原始的研究具有巨大的潜力，可以为我们对影响多细胞生物基因调节的细胞细胞通信网络的理解增加另一个维度。