Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
Nature. 2020 Jul;583(7818):711-719. doi: 10.1038/s41586-020-2077-3. Epub 2020 Jul 29.
Many proteins regulate the expression of genes by binding to specific regions encoded in the genome. Here we introduce a new data set of RNA elements in the human genome that are recognized by RNA-binding proteins (RBPs), generated as part of the Encyclopedia of DNA Elements (ENCODE) project phase III. This class of regulatory elements functions only when transcribed into RNA, as they serve as the binding sites for RBPs that control post-transcriptional processes such as splicing, cleavage and polyadenylation, and the editing, localization, stability and translation of mRNAs. We describe the mapping and characterization of RNA elements recognized by a large collection of human RBPs in K562 and HepG2 cells. Integrative analyses using five assays identify RBP binding sites on RNA and chromatin in vivo, the in vitro binding preferences of RBPs, the function of RBP binding sites and the subcellular localization of RBPs, producing 1,223 replicated data sets for 356 RBPs. We describe the spectrum of RBP binding throughout the transcriptome and the connections between these interactions and various aspects of RNA biology, including RNA stability, splicing regulation and RNA localization. These data expand the catalogue of functional elements encoded in the human genome by the addition of a large set of elements that function at the RNA level by interacting with RBPs.
许多蛋白质通过结合基因组中编码的特定区域来调节基因的表达。在这里，我们介绍了一个新的人类基因组 RNA 元件数据集，这些 RNA 元件是作为 DNA 元件百科全书（ENCODE）项目第三阶段的一部分被识别出来的。这类调节元件只有在转录成 RNA 时才起作用，因为它们作为 RNA 结合蛋白（RBPs）的结合位点，控制着转录后过程，如剪接、切割和多聚腺苷酸化，以及 mRNA 的编辑、定位、稳定性和翻译。我们描述了在 K562 和 HepG2 细胞中大量人类 RBPs 识别的 RNA 元件的映射和特征。使用五种检测方法的综合分析鉴定了体内 RNA 和染色质上的 RBP 结合位点、RBPs 的体外结合偏好、RBP 结合位点的功能以及 RBPs 的亚细胞定位，为 356 个 RBPs 产生了 1223 个复制数据集。我们描述了 RBP 在整个转录组中的结合谱，以及这些相互作用与 RNA 生物学的各个方面（包括 RNA 稳定性、剪接调控和 RNA 定位）之间的联系。这些数据通过添加一组在 RNA 水平上通过与 RBPs 相互作用起作用的大量元件，扩展了人类基因组中功能元件的目录。
