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RNA-Binding Protein Musashi1 Is a Central Regulator of Adhesion Pathways in Glioblastoma

Authors :
Andrew D. Smith
Mei Qiao
Myriam Gorospe
Helder I. Nakaya
Kotb Abdelmohsen
Patrícia R. Araújo
Jernej Ule
Raquel de Sousa Abreu
Caspar D. Kühnöl
Emad Bahrami-Samani
Philip J. Uren
Jennifer L. Martindale
Bruna R. Correa
Rebecca Pötschke
Dat T. Vo
Luiz O. F. Penalva
Suzanne C. Burns
Source :
Molecular and Cellular Biology. 35:2965-2978
Publication Year :
2015
Publisher :
Informa UK Limited, 2015.

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 individual-nucleotide 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.

Details

ISSN :
10985549
Volume :
35
Database :
OpenAIRE
Journal :
Molecular and Cellular Biology
Accession number :
edsair.doi.dedup.....2faa8a53565cde21286b41898581fd2b
Full Text :
https://doi.org/10.1128/mcb.00410-15