Genetic models for exRNA communication

exRNA通讯的遗传模型

• 批准号: 9462406
• 负责人: MICHAEL T MCMANUS
• 金额: $ 22.84万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9462406
• 关键词: Address; Biogenesis; Biological; Body Fluids; Caenorhabditis elegans; Cell Culture Techniques; Cells; Communication; Genes; Genetic Models; Goals; Individual; Knowledge; Medicine; MicroRNAs; Modeling; Population Heterogeneity; RNA; Tissues; Transfer RNA; U-Series Cooperative Agreements; Untranslated RNA; Validation; Whole Organism; Work; cell type; extracellular; novel; public health relevance; uptake

DESCRIPTION (provided by applicant): Accumulating evidence indicates that some of the many RNAs identified in body fluids and cell culture medium may be functional. Although proof-of-principle and validation projects have demonstrated cell-to-cell RNA transfer, not a single mammalian extracellular RNA has been demonstrated to enter and function in a target cell, at least in a biologically relevant and robust manner. Moreover exRNA uptake has yet to be characterized in a primary mammalian model. We do not know the functional consequences for exRNA uptake, or for that matter, the consequences of uptake deficiency. Studies over the last few years have illustrated a large and diverse population of exRNAs, including microRNA and long non-coding RNA (IncRNAs) - but we have no reference set for specific tissues, nor do we have an understanding of which exRNAs are functionally important for those tissues. Likewise, we do not have any idea of the genes involved, save for two homologs for the C. elegans SID-1 exRNA transporter that are still awaiting full characterization. Whether all, or only a few cell types can uptake exRNA also remains a complete mystery. This U19 Cooperative Agreement directly addresses critical gaps in our knowledge of the fundamental principles of exRNA biogenesis, distribution, uptake, and function.

描述（由申请人提供）：越来越多的证据表明，在体液和细胞培养基中鉴定的许多 RNA 中的一些可能具有功能。尽管原理验证和验证项目已经证明了细胞间 RNA 转移，但没有任何一种哺乳动物细胞外 RNA 被证明可以进入靶细胞并在其中发挥作用，至少是以生物学相关和稳健的方式。此外，初级哺乳动物模型中的 exRNA 摄取尚未得到表征。我们不知道 exRNA 摄取的功能后果，或者摄取不足的后果。过去几年的研究表明存在大量不同的 exRNA，包括 microRNA 和长链非编码 RNA (IncRNA)，但我们没有特定组织的参考集，也不了解哪些 exRNA 具有重要的功能对于那些组织。同样，我们对所涉及的基因一无所知，除了线虫 SID-1 exRNA 转运蛋白的两个同源基因仍在等待全面表征之外。是所有细胞类型还是只有少数细胞类型可以摄取 exRNA 仍然是一个谜。这项 U19 合作协议直接解决了我们对 exRNA 生物发生、分布、摄取和功能基本原理的认识中的关键差距。

项目成果

miR-205 is a critical regulator of lacrimal gland development.

• DOI: 10.1016/j.ydbio.2017.05.012
• 发表时间: 2017-07-01
• 期刊: DEVELOPMENTAL BIOLOGY
• 影响因子: 2.7
• 作者: Farmer, D'Juan T.;Finley, Jennifer K.;Chen, Feeling Y.;Tarifeno-Saldivia, Estefania;McNamara, Nancy A.;Knox, Sarah M.;McManus, Michael T.
• 通讯作者: McManus, Michael T.