RNA 结合蛋白在人类细胞中对 RNA 编辑的调控。
Regulation of RNA editing by RNA-binding proteins in human cells.
机构信息
1Department of Bioengineering, University of California Los Angeles, Los Angeles, CA 90095 USA.
2Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, CA 90095 USA.
出版信息
Commun Biol. 2019 Jan 14;2:19. doi: 10.1038/s42003-018-0271-8. eCollection 2019.
Adenosine-to-inosine (A-to-I) editing, mediated by the ADAR enzymes, diversifies the transcriptome by altering RNA sequences. Recent studies reported global changes in RNA editing in disease and development. Such widespread editing variations necessitate an improved understanding of the regulatory mechanisms of RNA editing. Here, we study the roles of >200 RNA-binding proteins (RBPs) in mediating RNA editing in two human cell lines. Using RNA-sequencing and global protein-RNA binding data, we identify a number of RBPs as key regulators of A-to-I editing. These RBPs, such as TDP-43, DROSHA, NF45/90 and Ro60, mediate editing through various mechanisms including regulation of expression, interaction with ADAR1, and binding to Alu elements. We highlight that editing regulation by Ro60 is consistent with the global up-regulation of RNA editing in systemic lupus erythematosus. Additionally, most key editing regulators act in a cell type-specific manner. Together, our work provides insights for the regulatory mechanisms of RNA editing.
腺苷到次黄嘌呤（A-to-I）编辑，由 ADAR 酶介导，通过改变 RNA 序列使转录组多样化。最近的研究报告了疾病和发育过程中 RNA 编辑的全局变化。这种广泛的编辑变化需要更好地理解 RNA 编辑的调控机制。在这里，我们在两种人类细胞系中研究了 200 多种 RNA 结合蛋白（RBP）在介导 RNA 编辑中的作用。我们使用 RNA 测序和全局蛋白质 RNA 结合数据，鉴定了许多 RBP 作为 A-to-I 编辑的关键调节剂。这些 RBP，如 TDP-43、DROSHA、NF45/90 和 Ro60，通过各种机制介导编辑，包括调节表达、与 ADAR1 相互作用以及与 Alu 元件结合。我们强调，Ro60 的编辑调控与全身性红斑狼疮中 RNA 编辑的全局上调一致。此外，大多数关键编辑调节剂以细胞类型特异性方式起作用。总之，我们的工作为 RNA 编辑的调控机制提供了新的见解。
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