Genomic analyses of Musashi1 downstream targets show a strong association with cancer-related processes

Raquel de Sousa Abreu, Patricia C. Sanchez-Diaz, Christine Vogel, Suzanne C. Burns, Daijin Ko, Tarea L. Burton, Dat T. Vo, Soudhamini Chennasamudaram, Shu Yun Le, Bruce A. Shapiro, Luiz O F Penalva

Research output: Contribution to journalArticle

Abstract

Musashi1 (Msi1) is a highly conserved RNA-binding protein with pivotal functions in stem cell maintenance, nervous system development, and tumorigenesis. Despite its importance, only three direct mRNA targets have been characterized so far: m-numb, CDKN1A, and c-mos. Msi1 has been shown to affect their translation by binding to short elements located in the 3′-untranslated region. To better understand Msi1 functions, we initially performed an RIP-Chip analysis in HEK293T cells; this method consists of isolation of specific RNA-protein complexes followed by identification of the RNA component via microarrays. A group of 64 mRNAs was found to be enriched in the Msi1-associated population compared with controls. These genes belong to two main functional categories pertinent to tumorigenesis: 1) cell cycle, cell proliferation, cell differentiation, and apoptosis and 2) protein modification (including ubiquitination and ubiquitin cycle). To corroborate our findings, we examined the impact of Msi1 expression on both mRNA (transcriptomic) and protein (proteomic) expression levels. Genes whose mRNA levels were affected by Msi1 expression have a Gene Ontology distribution similar to RIP-Chip results, reinforcing Msi1 participation in cancer-related processes. The proteomics study revealed that Msi1 can have either positive or negative effects on gene expression of its direct targets. In summary, our results indicate that Msi1 affects a network of genes and could function as a master regulator during development and tumor formation.

Original languageEnglish (US)
Pages (from-to)12125-12135
Number of pages11
JournalJournal of Biological Chemistry
Volume284
Issue number18
DOIs
StatePublished - May 1 2009

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Genes
Association reactions
Messenger RNA
Proteomics
Neoplasms
Carcinogenesis
RNA
Gene Ontology
Proteins
RNA-Binding Proteins
Gene Regulatory Networks
Ubiquitination
Cell proliferation
Neurology
3' Untranslated Regions
Microarrays
Ubiquitin
Stem cells
Gene expression
Nervous System

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

de Sousa Abreu, R., Sanchez-Diaz, P. C., Vogel, C., Burns, S. C., Ko, D., Burton, T. L., ... Penalva, L. O. F. (2009). Genomic analyses of Musashi1 downstream targets show a strong association with cancer-related processes. Journal of Biological Chemistry, 284(18), 12125-12135. https://doi.org/10.1074/jbc.M809605200

Genomic analyses of Musashi1 downstream targets show a strong association with cancer-related processes. / de Sousa Abreu, Raquel; Sanchez-Diaz, Patricia C.; Vogel, Christine; Burns, Suzanne C.; Ko, Daijin; Burton, Tarea L.; Vo, Dat T.; Chennasamudaram, Soudhamini; Le, Shu Yun; Shapiro, Bruce A.; Penalva, Luiz O F.

In: Journal of Biological Chemistry, Vol. 284, No. 18, 01.05.2009, p. 12125-12135.

Research output: Contribution to journalArticle

de Sousa Abreu, R, Sanchez-Diaz, PC, Vogel, C, Burns, SC, Ko, D, Burton, TL, Vo, DT, Chennasamudaram, S, Le, SY, Shapiro, BA & Penalva, LOF 2009, 'Genomic analyses of Musashi1 downstream targets show a strong association with cancer-related processes', Journal of Biological Chemistry, vol. 284, no. 18, pp. 12125-12135. https://doi.org/10.1074/jbc.M809605200
de Sousa Abreu, Raquel ; Sanchez-Diaz, Patricia C. ; Vogel, Christine ; Burns, Suzanne C. ; Ko, Daijin ; Burton, Tarea L. ; Vo, Dat T. ; Chennasamudaram, Soudhamini ; Le, Shu Yun ; Shapiro, Bruce A. ; Penalva, Luiz O F. / Genomic analyses of Musashi1 downstream targets show a strong association with cancer-related processes. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 18. pp. 12125-12135.
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