title: Transcriptome-wide targets of alternative splicing by RBM4 and possible role in cancer.
abstract: This study determined transcriptome-wide targets of the splicing factor RBM4 using Affymetrix GeneChip(®) Human Exon 1.0 ST Arrays and HeLa cells treated with RBM4-specific siRNA. This revealed 238 transcripts that were targeted for alternative splicing. Cross-linking and immunoprecipitation experiments identified 945 RBM4 targets in mouse HEK293 cells, 39% of which were ascribed to "alternative splicing" by in silico pathway analysis. Mouse embryonic stem cells transfected with Rbm4 siRNA hairpins exhibited reduced colony numbers and size consistent with involvement of RBM4 in cell proliferation. RBM4 cDNA probing of a cancer cDNA array involving 18 different tumor types from 13 different tissues and matching normal tissue found overexpression of RBM4 mRNA (p<0.01) in cervical, breast, lung, colon, ovarian and rectal cancers. Many RBM4 targets we identified have been implicated in these cancers. In conclusion, our findings reveal transcriptome-wide targets of RBM4 and point to potential cancer-related targets and mechanisms that may involve RBM4.
authors.affiliation: Basic & Clinical Genomics Laboratory, School of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, New South Wales, Australia. Electronic address: andrea.markus@med.uni-goettingen.de.
authors.forename: M Andrea
authors.initials: MA
authors.lastname: Markus
authors.affiliation: School of Mathematics and Statistics, The University of Sydney, Sydney, New South Wales, Australia. Electronic address: jean.yang@sydney.edu.au.
authors.forename: Yee Hwa J
authors.initials: YH
authors.lastname: Yang
authors.affiliation: Basic & Clinical Genomics Laboratory, School of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, New South Wales, Australia. Electronic address: brian.morris@sydney.edu.au.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Morris
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002478:Cells, Cultured; D019295:Computational Biology; D053595:Embryonic Stem Cells; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D059467:Transcriptome
chemical_list: C473692:RBM4 protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins
keywords: CLIP; Cancer; Exon arrays; RNA binding proteins; RNA splicing