TY - JOUR
T1 - RNA-binding protein musashi1 is a central regulator of adhesion pathways in glioblastoma
AU - Uren, Philip J.
AU - Vo, Dat T.
AU - de Araujo, Patricia Rosa
AU - Pötschke, Rebecca
AU - Burns, Suzanne C.
AU - Bahrami-Samani, Emad
AU - Qiao, Mei
AU - Abreu, Raquel de Sousa
AU - Nakaya, Helder I.
AU - Correa, Bruna R.
AU - Kühnöl, Caspar
AU - Ule, Jernej
AU - Martindale, Jennifer L.
AU - Abdelmohsen, Kotb
AU - Gorospe, Myriam
AU - Smith, Andrew D.
AU - Penalva, Luiz O.F.
N1 - Publisher Copyright:
© 2015, American Society for Microbiology.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
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U2 - 10.1128/MCB.00410-15
DO - 10.1128/MCB.00410-15
M3 - Article
C2 - 26100017
AN - SCOPUS:84938864372
SN - 0270-7306
VL - 35
SP - 2965
EP - 2978
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 17
ER -