Genetic models for exRNA communication

描述(由申请人提供)：越来越多的证据表明，在体液和细胞培养液中发现的许多RNA中，有一些可能具有功能。尽管原则证明和验证项目已经证明了细胞间的RNA转移，但还没有一个哺乳动物细胞外RNA被证明进入目标细胞并在其中发挥作用，至少在生物学上是相关的和强大的方式。此外，外源RNA的摄取还没有在主要的哺乳动物模型中被表征。我们不知道外源RNA摄取的功能后果，也不知道摄取不足的后果。过去几年的研究显示了大量不同的exRNAs，包括microRNA和长非编码RNA(IncRNAs)-但我们没有针对特定组织的参考集，也不了解哪些exRNAs对这些组织的功能重要。同样，除了线虫SID-1出口RNA转运体的两个同源基因仍在等待全面鉴定外，我们对涉及的基因一无所知。是否所有或只有几种细胞类型能够摄取exRNA也是一个完全的谜。这份U19合作协议直接解决了我们对exRNA生物发生、分布、摄取和功能基本原则的认识中的关键空白。

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.