DIAC Core

在过去的十年里，人们在包括血浆和血清在内的体液中发现了miRNAs。这导致了一种假设，即RNA扮演着细胞外信号分子的角色。现在清楚的是，这些rna不仅存在于外体或其他小泡中，而且还存在于与载体蛋白结合的外部小泡中，例如Argonaute(Ago)蛋白。 在囊泡介导的RNA信号中，囊泡由多种细胞分泌，并含有可被其他细胞摄取的RNA(如mRNA、miRNA和其他ncRNA)。强有力的证据表明，它们可以在其他细胞中发挥作用。在无泡RNA信号中，exRNAs(如siRNA和miRNA)也可以通过特定的受体或通道跨细胞膜运输，但这种方式的证据要弱得多。。通过RNA传递的信号具有自分泌、旁分泌或内分泌信号的潜能，因此在许多生物过程中具有重要的潜在意义。现在很清楚，大多数体液中含有miRNA和其他ncRNA，而且，这些exRNAs是各种病理状态的标志，包括癌症和毒性。 虽然以前的研究已经观察到了广泛存在的信号exRNA，但仍不完全清楚源细胞如何和为什么发射RNA，它们是如何运输的，以及靶细胞如何摄取和解释RNA。目前也不清楚何时以及为什么需要胞外包涵体，以及包涵体如何影响生物功能。为了全面了解这种细胞间通信的复杂机制，需要一套参考图谱，即exRNA图谱，其中包括结合exRNA的蛋白质和其他载体分子的图谱，以及外体和体液的RNA含量图谱。为了能够构建exRNA图谱，我们将构建一个自动化的en-exRNA管道，通过调整现有的用于mRNAs和miRNAs的RNA-SEQ工作流程来创建一个exRNA图谱数据库，并为社区和创建和exRNA图谱知识库开发先进的enexRNA分析方法和工具。

The last decade has seen the discovery of miRNAs in body fluids including plasma and serum. This lead to the hypothesis that RNAs play roles as extracellular signaling molecules . It is now clear that these RNAs exist not only in exosomes or other vesicles, but also outside vesicles bound to carrier proteins, such as Argonaute (Ago) proteins In vesicle-mediated RNA signaling, the vesicles are secreted by a large variety of cells, and contain RNAs (e.g. mRNA, miRNA and other ncRNA) that can be taken up by other cells. Strong evidence shows that they can be functional in other cells . In vesicle-free RNA signaling, exRNAs (e.g. siRNA and miRNA) could also be transported across cell membranes by specific receptors or channels, but evidence is much weaker for this mode . . Signaling via RNAs has the potential to play roles as autocrine, paracrine or endocrine signaling , and is therefore of great potential significance in many biological processes. It is now clear that most body fluids contain miRNA and other ncRNAs Moreover, these exRNAs are markers for various pathological states, including cancers and toxicity. Although previous studies have observed widespread signaling exRNAs, it is still not fully understood how and why source cells emit RNA, how they are transported, and how the target cells uptake and interpret the RNAs. It is also not clear when and why exosomal inclusion is needed, and how the inclusion affects biological function. In order to develop a comprehensive understanding of the complex mechanisms of this intercellular communication, a set of reference maps, an exRNA Atlas, is needed including a map of proteins and other carrier molecules that bind exRNA, as well as profiles of RNA content of exosomes and body fluids. To enable ^ the construction of an exRNA Atlas we will construct an automated en-exRNA pipeline for creating an exRNA Atlas Database by adapting existing RNA-seq workflows for mRNAs and miRNAs and develop advanced enexRNA analysis methods and tools for the community and for creating and exRNA Atlas Knowledge Base.