Department of Biochemistry and Molecular Genetics, RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Nucleic Acids Res. 2019 Jan 25;47(2):570-581. doi: 10.1093/nar/gky1185.
RNA-binding proteins (RBPs) control and coordinate each stage in the life cycle of RNAs. Although in vivo binding sites of RBPs can now be determined genome-wide, most studies typically focused on individual RBPs. Here, we examined a large compendium of 114 high-quality transcriptome-wide in vivo RBP-RNA cross-linking interaction datasets generated by the same protocol in the same cell line and representing 64 distinct RBPs. Comparative analysis of categories of target RNA binding preference, sequence preference, and transcript region specificity was performed, and identified potential posttranscriptional regulatory modules, i.e. specific combinations of RBPs that bind to specific sets of RNAs and targeted regions. These regulatory modules represented functionally related proteins and exhibited distinct differences in RNA metabolism, expression variance, as well as subcellular localization. This integrative investigation of experimental RBP-RNA interaction evidence and RBP regulatory function in a human cell line will be a valuable resource for understanding the complexity of post-transcriptional regulation.
RNA 结合蛋白 (RBPs) 控制和协调 RNA 生命周期的各个阶段。尽管现在可以在全基因组范围内确定 RBP 的体内结合位点，但大多数研究通常集中在单个 RBP 上。在这里，我们研究了一个由同一种细胞系中相同方案生成的 114 个高质量的转录组范围内体内 RBP-RNA 交联相互作用数据集的大型纲要，这些数据集代表了 64 个不同的 RBP。对目标 RNA 结合偏好、序列偏好和转录本区域特异性的类别进行了比较分析，并确定了潜在的转录后调控模块，即特定的 RBP 组合与特定的 RNA 集和靶向区域结合。这些调控模块代表了功能相关的蛋白质，在 RNA 代谢、表达变异以及亚细胞定位方面表现出明显的差异。这种对人类细胞系中实验性 RBP-RNA 相互作用证据和 RBP 调节功能的综合研究，将成为理解转录后调控复杂性的宝贵资源。
