Oncotarget

Research Papers:

Genome-wide identification of Wig-1 mRNA targets by RIP-Seq analysis

Cinzia Bersani, Mikael Huss, Stefania Giacomello, Li-Di Xu, Julie Bianchi, Sofi Eriksson, Fredrik Jerhammar, Andrey Alexeyenko, Anna Vilborg, Joakim Lundeberg, Weng-Onn Lui and Klas G. Wiman _

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Oncotarget. 2016; 7:1895-1911. https://doi.org/10.18632/oncotarget.6557

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Abstract

Cinzia Bersani1, Mikael Huss2, Stefania Giacomello2, Li-Di Xu1, Julie Bianchi1, Sofi Eriksson1, Fredrik Jerhammar1, Andrey Alexeyenko3, Anna Vilborg4, Joakim Lundeberg2, Weng-Onn Lui1, Klas G. Wiman1

1Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Stockholm, Sweden

2Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology, Solna, Sweden

3Department of Microbiology, Tumour and Cell biology, Bioinformatics Infrastructure for Life Sciences, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden

4Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA

Correspondence to:

Klas G. Wiman, e-mail: Klas.Wiman@ki.se

Keywords: Wig-1, AREs, RIP-Seq, cell cycle, p53

Received: June 24, 2015     Accepted: November 15, 2015     Published: December 11, 2015

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.


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