RNA-binding protein musashi1 is a central regulator of adhesion pathways in glioblastoma

Philip J. Uren, Dat T. Vo, Patricia Rosa de Araujo, Rebecca Pötschke, Suzanne C. Burns, Emad Bahrami-Samani, Mei Qiao, Raquel de Sousa Abreu, Helder I. Nakaya, Bruna R. Correa, Caspar Kühnöl, Jernej Ule, Jennifer L. Martindale, Kotb Abdelmohsen, Myriam Gorospe, Andrew D. Smith, Luiz O.F. Penalva

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

The conserved RNA-binding protein Musashi1 (MSI1) has emerged as a key oncogenic factor in numerous solid tumors, including glioblastoma. However, its mechanism of action has not yet been established comprehensively. To identify its target genes comprehensively and determine the main routes by which it influences glioblastoma phenotypes, we conducted individualnucleotide resolution cross-linking and immunoprecipitation (iCLIP) experiments. We confirmed that MSI1 has a preference for UAG sequences contained in a particular structural context, especially in 3= untranslated regions. Although numerous binding sites were also identified in intronic sequences, our RNA transcriptome sequencing analysis does not favor the idea that MSI1 is a major regulator of splicing in glioblastoma cells. MSI1 target mRNAs encode proteins that function in multiple pathways of cell proliferation and cell adhesion. Since these associations indicate potentially new roles for MSI1, we investigated its impact on glioblastoma cell adhesion, morphology, migration, and invasion. These processes are known to underpin the spread and relapse of glioblastoma, in contrast to other tumors where metastasis is the main driver of recurrence and progression.

Original languageEnglish (US)
Pages (from-to)2965-2978
Number of pages14
JournalMolecular and cellular biology
Volume35
Issue number17
DOIs
StatePublished - 2015
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Uren, P. J., Vo, D. T., de Araujo, P. R., Pötschke, R., Burns, S. C., Bahrami-Samani, E., Qiao, M., Abreu, R. D. S., Nakaya, H. I., Correa, B. R., Kühnöl, C., Ule, J., Martindale, J. L., Abdelmohsen, K., Gorospe, M., Smith, A. D., & Penalva, L. O. F. (2015). RNA-binding protein musashi1 is a central regulator of adhesion pathways in glioblastoma. Molecular and cellular biology, 35(17), 2965-2978. https://doi.org/10.1128/MCB.00410-15