Genetic models for exRNA communication

描述（由申请人提供）：越来越多的证据表明，体液和细胞培养基中发现的许多rna中的一些可能是功能性的。尽管原理验证和验证项目已经证明了细胞间RNA转移，但没有一种哺乳动物细胞外RNA被证明进入靶细胞并在靶细胞中发挥作用，至少以生物学相关和稳健的方式。此外，exRNA摄取尚未在初级哺乳动物模型中表征。我们不知道exRNA摄取的功能后果，也不知道摄取不足的后果。过去几年的研究已经说明了大量不同种类的exRNAs，包括microRNA和长链非编码RNA (IncRNAs)，但我们没有特定组织的参考集，也不知道哪些exRNAs对这些组织有重要的功能。同样，我们也不知道涉及的基因，除了秀丽隐杆线虫SID-1 exRNA转运体的两个同源基因，它们仍在等待完全的鉴定。是否所有或只有少数细胞类型可以摄取exRNA仍然是一个完全的谜。这份U19合作协议直接解决了我们在exRNA生物发生、分布、摄取和功能的基本原理方面的关键空白。

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 typs 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.