title: RNA-Binding Protein Musashi1 Is a Central Regulator of Adhesion Pathways in Glioblastoma.
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.
authors.affiliation: Molecular and Computational Biology Section, Division of Biological Sciences, University of Southern California, Los Angeles, California, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Uren
authors.affiliation: Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Dat T
authors.initials: DT
authors.lastname: Vo
authors.affiliation: Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Patricia Rosa
authors.initials: PR
authors.lastname: de Araujo
authors.affiliation: University Medical Center, Department of Children's Hospital, Halle (Saale), Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Pötschke
authors.affiliation: Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Burns
authors.affiliation: Molecular and Computational Biology Section, Division of Biological Sciences, University of Southern California, Los Angeles, California, USA.
authors.forename: Emad
authors.initials: E
authors.lastname: Bahrami-Samani
authors.affiliation: Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Qiao
authors.affiliation: Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Raquel
authors.initials: R
authors.lastname: de Sousa Abreu
authors.affiliation: School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil Department of Pathology, Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, Georgia, USA.
authors.forename: Helder I
authors.initials: HI
authors.lastname: Nakaya
authors.affiliation: Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Bruna R
authors.initials: BR
authors.lastname: Correa
authors.affiliation: University Medical Center, Department of Children's Hospital, Halle (Saale), Germany.
authors.forename: Caspar
authors.initials: C
authors.lastname: Kühnöl
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College London, London, United Kingdom.
authors.forename: Jernej
authors.initials: J
authors.lastname: Ule
authors.affiliation: Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Martindale
authors.affiliation: Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: Kotb
authors.initials: K
authors.lastname: Abdelmohsen
authors.affiliation: Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.affiliation: Molecular and Computational Biology Section, Division of Biological Sciences, University of Southern California, Los Angeles, California, USA andrewds@usc.edu penalva@uthscsa.edu.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Smith
authors.affiliation: Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA andrewds@usc.edu penalva@uthscsa.edu.
authors.forename: Luiz O F
authors.initials: LO
authors.lastname: Penalva
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017398:Alternative Splicing / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D017423:Sequence Analysis, RNA
chemical_list: D020413:3' Untranslated Regions; C491297:MSI1 protein, human; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins