title: Genome-wide analysis of YB-1-RNA interactions reveals a novel role of YB-1 in miRNA processing in glioblastoma multiforme.
abstract: 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.
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Shuai-Lai
authors.initials: SL
authors.lastname: Wu
authors.affiliation: Shanghai Center for Plant Stress Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201602, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Feng-Yang
authors.initials: FY
authors.lastname: Zong
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Shi-Rong
authors.initials: SR
authors.lastname: Mu
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Shanghai Institute of Neurosurgery, Chang Zheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Neurology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Shuwei
authors.initials: S
authors.lastname: Qiu
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Neurology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Neurosurgery, Shanghai Institute of Neurosurgery, Chang Zheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Juxiang
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China jyhui@sibcb.ac.cn.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Hui
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D023281:Genomics; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D057809:HEK293 Cells; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000378:metabolism; D043244:Ribonuclease III / Q000037:antagonists & inhibitors; D017423:Sequence Analysis, RNA; D051840:Y-Box-Binding Protein 1 / Q000378:metabolism*
chemical_list: C474043:DGCR8 protein, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D012313:RNA; C517918:DROSHA protein, human; D043244:Ribonuclease III