title: Genome-wide identification of Wig-1 mRNA targets by RIP-Seq analysis.
abstract: RNA-binding proteins (RBPs) play important roles in the regulation of gene expression through a variety of post-transcriptional mechanisms. The p53-induced RBP Wig-1 (Zmat3) binds RNA through its zinc finger domains and enhances stability of p53 and N-Myc mRNAs and decreases stability of FAS mRNA. To identify novel Wig-1-bound RNAs, we performed RNA-immunoprecipitation followed by high-throughput sequencing (RIP-Seq) in HCT116 and Saos-2 cells. We identified 286 Wig-1-bound mRNAs common between the two cell lines. Sequence analysis revealed that AU-rich elements (AREs) are highly enriched in the 3'UTR of these Wig-1-bound mRNAs. Network enrichment analysis showed that Wig-1 preferentially binds mRNAs involved in cell cycle regulation. Moreover, we identified a 2D Wig-1 binding motif in HIF1A mRNA. Our findings confirm that Wig-1 is an ARE-BP that regulates cell cycle-related processes and provide a novel view of how Wig-1 may bind mRNA through a putative structural motif. We also significantly extend the repertoire of Wig-1 target mRNAs. Since Wig-1 is a transcriptional target of the tumor suppressor p53, these results have implications for our understanding of p53-dependent stress responses and tumor suppression.
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Stockholm, Sweden.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Bersani
authors.affiliation: Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology, Solna, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Huss
authors.affiliation: Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology, Solna, Sweden.
authors.forename: Stefania
authors.initials: S
authors.lastname: Giacomello
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Stockholm, Sweden.
authors.forename: Li-Di
authors.initials: LD
authors.lastname: Xu
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Stockholm, Sweden.
authors.forename: Julie
authors.initials: J
authors.lastname: Bianchi
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Stockholm, Sweden.
authors.forename: Sofi
authors.initials: S
authors.lastname: Eriksson
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Stockholm, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Jerhammar
authors.affiliation: Department of Microbiology, Tumour and Cell biology, Bioinformatics Infrastructure for Life Sciences, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Andrey
authors.initials: A
authors.lastname: Alexeyenko
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Vilborg
authors.affiliation: Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology, Solna, Sweden.
authors.forename: Joakim
authors.initials: J
authors.lastname: Lundeberg
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Stockholm, Sweden.
authors.forename: Weng-Onn
authors.initials: WO
authors.lastname: Lui
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Stockholm, Sweden.
authors.forename: Klas G
authors.initials: KG
authors.lastname: Wiman
mesh_terms: D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D045325:HCT116 Cells; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D047468:Immunoprecipitation; D009687:Nuclear Proteins / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics*; D016601:RNA-Binding Proteins; D060888:Real-Time Polymerase Chain Reaction; D020218:Response Elements / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C436503:ZMAT3 protein, human
keywords: AREs; RIP-Seq; Wig-1; cell cycle; p53