title: Global regulation of alternative RNA splicing by the SR-rich protein RBM39.
abstract: RBM39 is a serine/arginine-rich RNA-binding protein that is highly homologous to the splicing factor U2AF65. However, the role of RBM39 in alternative splicing is poorly understood.
  
  
  
  In this study, RBM39-mediated global alternative splicing was investigated using RNA-Seq and genome-wide RBM39-RNA interactions were mapped via cross-linking and immunoprecipitation coupled with deep sequencing (CLIP-Seq) in wild-type and RBM39-knockdown MCF-7 cells.
  
  
  
  RBM39 was involved in the up- or down-regulation of the transcript levels of various genes. Hundreds of alternative splicing events regulated by endogenous RBM39 were identified. The majority of these events were cassette exons. Genes containing RBM39-regulated alternative exons were found to be linked to G2/M transition, cellular response to DNA damage, adherens junctions and endocytosis. CLIP-Seq analysis showed that the binding site of RBM39 was mainly in proximity to 5' and 3' splicing sites. Considerable RBM39 binding to mRNAs encoding proteins involved in translation was observed. Of particular importance, ~20% of the alternative splicing events that were significantly regulated by RBM39 were similarly regulated by U2AF65.
  
  
  
  RBM39 is extensively involved in alternative splicing of RNA and helps regulate transcript levels. RBM39 may modulate alternative splicing similarly to U2AF65 by either directly binding to RNA or recruiting other splicing factors, such as U2AF65.
  
  
  
  The current study offers a genome-wide view of RBM39's regulatory function in alternative splicing. RBM39 may play important roles in multiple cellular processes by regulating both alternative splicing of RNA molecules and transcript levels.
authors.affiliation: Beijing Institute of Biotechnology, 27 Taiping Rd, Haidian District, Beijing 100850, China.
authors.forename: Sanyue
authors.initials: S
authors.lastname: Mai
authors.affiliation: General Navy Hospital of PLA, 6 Fucheng Rd, Haidian District, Beijing 100037, China.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Qu
authors.affiliation: Beijing Institute of Biotechnology, 27 Taiping Rd, Haidian District, Beijing 100850, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Beijing Institute of Biotechnology, 27 Taiping Rd, Haidian District, Beijing 100850, China.
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Beijing Institute of Biotechnology, 27 Taiping Rd, Haidian District, Beijing 100850, China. Electronic address: cao_c@sohu.com.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cao
authors.affiliation: Beijing Institute of Biotechnology, 27 Taiping Rd, Haidian District, Beijing 100850, China. Electronic address: liux931932@163.com.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
mesh_terms: D022005:Adherens Junctions / Q000235:genetics; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001120:Arginine / Q000378:metabolism; D001665:Binding Sites; D004249:DNA Damage; D015536:Down-Regulation; D004705:Endocytosis / Q000235:genetics; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D061986:MCF-7 Cells; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D000072668:Splicing Factor U2AF / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C084105:HCC1 autoantigen; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000072668:Splicing Factor U2AF; C000607494:U2AF2 protein, human; D012694:Serine; D001120:Arginine
keywords: Alternative splicing; CLIP-Seq; RBM39; RNA-Seq; U2AF65