Genome-wide analysis of YB-1-RNA interactions reveals a novel role of YB-1 in miRNA processing in glioblastoma multiforme.
Genome-wide analysis of YB-1-RNA interactions reveals a novel role of YB-1 in miRNA processing in glioblastoma multiforme.
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YB-1-RNA 相互作用的全基因组分析揭示了 YB-1 在多形性胶质母细胞瘤 miRNA 加工中的新作用
DOI：
10.1093/nar/gkv779
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发表时间：
2015-09-30
影响因子：
14.9
通讯作者：
Hui J
中科院分区：
文献类型：
--
作者：
Wu SL;Fu X;Huang J;Jia TT;Zong FY;Mu SR;Zhu H;Yan Y;Qiu S;Wu Q;Yan W;Peng Y;Chen J;Hui J
miRNA 表达的改变被认为在多种人类癌症中发挥着至关重要的作用；然而，导致 miRNA 表达失调的机制仍然难以捉摸。在这项研究中，我们报道了人类 Y 盒结合蛋白 (YB-1)，一种主要的 mRNA 包装蛋白，是多形性胶质母细胞瘤 (GBM) 中 miRNA 加工的新型调节剂。使用个体核苷酸分辨率交联免疫沉淀结合深度测序 (iCLIP-seq)，我们对体内 YB-1-RNA 相互作用进行了首次全基因组分析，发现 YB-1 优先识别 UYAUC 共有基序并与大多数编码基因转录本结合，包括前 mRNA 和成熟 mRNA。值得注意的是，我们的数据表明，YB-1 还广泛结合 pri-/pre-miR-29b-2 的末端环区域，并通过阻止微处理器和 Dicer 对其前体的募集来调节 miR-29b-2 的生物合成。此外，我们发现 YB-1 对 miR-29b 的下调（在 GBM 中上调）对于细胞增殖很重要。总之，我们的研究结果揭示了 YB-1 在调节非编码 RNA 表达方面的新功能，这对肿瘤发生具有重要意义。
Altered miRNA expression is believed to play a crucial role in a variety of human cancers; however, the mechanisms leading to the dysregulation of miRNA expression remain elusive. In this study, we report that the human Y box-binding protein (YB-1), a major mRNA packaging protein, is a novel modulator of miRNA processing in glioblastoma multiforme (GBM). Using individual nucleotide-resolution crosslinking immunoprecipitation coupled to deep sequencing (iCLIP-seq), we performed the first genome-wide analysis of the in vivo YB-1-RNA interactions and found that YB-1 preferentially recognizes a UYAUC consensus motif and binds to the majority of coding gene transcripts including pre-mRNAs and mature mRNAs. Remarkably, our data show that YB-1 also binds extensively to the terminal loop region of pri-/pre-miR-29b-2 and regulates the biogenesis of miR-29b-2 by blocking the recruitment of microprocessor and Dicer to its precursors. Furthermore, we show that down-regulation of miR-29b by YB-1, which is up-regulated in GBM, is important for cell proliferation. Together, our findings reveal a novel function of YB-1 in regulating non-coding RNA expression, which has important implications in tumorigenesis.