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A large-scale binding and functional map of human RNA-binding proteins
Nature ( IF 50.5 ) Pub Date : 2020-07-29 , DOI: 10.1038/s41586-020-2077-3
Eric L Van Nostrand 1, 2 , Peter Freese 3 , Gabriel A Pratt 1, 2, 4 , Xiaofeng Wang 5 , Xintao Wei 6 , Rui Xiao 1, 2, 7 , Steven M Blue 1, 2 , Jia-Yu Chen 1, 2 , Neal A L Cody 5 , Daniel Dominguez 8 , Sara Olson 6 , Balaji Sundararaman 1, 2 , Lijun Zhan 6 , Cassandra Bazile 8 , Louis Philip Benoit Bouvrette 5, 9 , Julie Bergalet 5 , Michael O Duff 6 , Keri E Garcia 1, 2 , Chelsea Gelboin-Burkhart 1, 2 , Myles Hochman 8 , Nicole J Lambert 8 , Hairi Li 1, 2 , Michael P McGurk 8 , Thai B Nguyen 1, 2 , Tsultrim Palden 8, 10 , Ines Rabano 1, 2 , Shashank Sathe 1, 2 , Rebecca Stanton 1, 2 , Amanda Su 8 , Ruth Wang 1, 2 , Brian A Yee 1, 2 , Bing Zhou 1, 2 , Ashley L Louie 1, 2 , Stefan Aigner 1, 2 , Xiang-Dong Fu 1, 2 , Eric Lécuyer 5, 9, 11 , Christopher B Burge 3, 8, 10 , Brenton R Graveley 6 , Gene W Yeo 1, 2, 4
Affiliation  

Many proteins regulate the expression of genes by binding to specific regions encoded in the genome1. 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. A combination of five assays is used to produce a catalogue of RNA elements to which RNA-binding proteins bind in human cells.

中文翻译:


人类 RNA 结合蛋白的大规模结合和功能图谱



许多蛋白质通过与基因组中编码的特定区域结合来调节基因的表达1。在这里,我们介绍了人类基因组中 RNA 元件的新数据集,这些数据集可被 RNA 结合蛋白 (RBP) 识别,该数据集是作为 DNA 元件百科全书 (ENCODE) 项目第三阶段的一部分生成的。这类调控元件只有在转录成 RNA 时才发挥作用,因为它们作为 RBP 的结合位点,控制转录后过程,如剪接、切割和聚腺苷酸化,以及 mRNA 的编辑、定位、稳定性和翻译。我们描述了 K562 和 HepG2 细胞中大量人类 RBP 识别的 RNA 元件的定位和表征。使用五种分析方法进行综合分析,确定体内 RNA 和染色质上的 RBP 结合位点、RBP 的体外结合偏好、RBP 结合位点的功能以及 RBP 的亚细胞定位,为 356 个 RBP 生成 1,223 个重复数据集。我们描述了整个转录组中 RBP 结合的范围,以及这些相互作用与 RNA 生物学各个方面(包括 RNA 稳定性、剪接调节和 RNA 定位)之间的联系。这些数据通过添加大量通过与 RBP 相互作用在 RNA 水平发挥作用的元件,扩展了人类基因组中编码的功能元件的目录。五种检测方法的组合用于生成人类细胞中 RNA 结合蛋白结合的 RNA 元件目录。
更新日期:2020-07-29
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