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Genome-wide identification of Wig-1 mRNA targets by RIP-Seq analysis
KTH, School of Biotechnology (BIO). KTH, Centres, Science for Life Laboratory, SciLifeLab.
KTH, School of Biotechnology (BIO). KTH, Centres, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0003-0738-1574
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2016 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 2, 1895-1911 p.Article in journal (Refereed) PublishedText
Abstract [en]

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.

Place, publisher, year, edition, pages
Impact Journals LLC , 2016. Vol. 7, no 2, 1895-1911 p.
Keyword [en]
Wig-1, AREs, RIP-Seq, cell cycle, p53
National Category
Cancer and Oncology
URN: urn:nbn:se:kth:diva-183336DOI: 10.18632/oncotarget.6557ISI: 000369951100062PubMedID: 26672765ScopusID: 2-s2.0-84957639027OAI: diva2:910090

QC 20160308

Available from: 2016-03-08 Created: 2016-03-07 Last updated: 2016-03-19Bibliographically approved

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Huss, MikaelGiacomello, StefaniaLundeberg, Joakim
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