Antagonism between the RNA-binding protein Musashi1 and miR-137 and its potential impact on neurogenesis and glioblastoma development

Mitzli X. Velasco, Adam Kosti, Gabriela D.A. Guardia, Marcia C. Santos, Allison Tegge, Mei Qiao, Bruna R.S. Correa, Greco Hernández, Erzsebet K Cearley, Pedro A.F. Galante, Luiz O Penalva

Research output: Contribution to journalArticle

Abstract

RNA-binding proteins (RBPs) and miRNAs are critical gene expression regulators that interact with one another in cooperative and antagonistic fashions. We identified Musashi1 (Msi1) and miR-137 as regulators of a molecular switch between self-renewal and differentiation. Msi1 and miR-137 have opposite expression patterns and functions, and Msi1 is repressed by miR-137. Msi1 is a stem-cell protein implicated in self-renewal while miR-137 functions as a proneuronal differentiation miRNA. In gliomas, miR-137 functions as a tumor suppressor while Msi1 is a prooncogenic factor. We suggest that the balance between Msi1 and miR-137 is a key determinant in cell fate decisions and disruption of this balance could contribute to neurodegenerative diseases and glioma development. Genomic analyses revealed that Msi1 and miR-137 share 141 target genes associated with differentiation, development, and morphogenesis. Initial results pointed out that these two regulators have an opposite impact on the expression of their target genes. Therefore, we propose an antagonistic model in which this network of shared targets could be either repressed by miR-137 or activated by Msi1, leading to different outcomes (self-renewal, proliferation, tumorigenesis).

Original languageEnglish (US)
Pages (from-to)768-782
Number of pages15
JournalRNA
Volume27
Issue number5
DOIs
StatePublished - Jan 1 2019

Fingerprint

RNA-Binding Proteins
Neurogenesis
Glioblastoma
MicroRNAs
Glioma
Morphogenesis
Neurodegenerative Diseases
Genes
Carcinogenesis
Stem Cells
Gene Expression
Neoplasms
Proteins

Keywords

  • Glioblastoma
  • MiR-137
  • MiRNA
  • Musashi1
  • Neurogenesis
  • RNA-binding protein

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Antagonism between the RNA-binding protein Musashi1 and miR-137 and its potential impact on neurogenesis and glioblastoma development. / Velasco, Mitzli X.; Kosti, Adam; Guardia, Gabriela D.A.; Santos, Marcia C.; Tegge, Allison; Qiao, Mei; Correa, Bruna R.S.; Hernández, Greco; Cearley, Erzsebet K; Galante, Pedro A.F.; Penalva, Luiz O.

In: RNA, Vol. 27, No. 5, 01.01.2019, p. 768-782.

Research output: Contribution to journalArticle

Velasco, MX, Kosti, A, Guardia, GDA, Santos, MC, Tegge, A, Qiao, M, Correa, BRS, Hernández, G, Cearley, EK, Galante, PAF & Penalva, LO 2019, 'Antagonism between the RNA-binding protein Musashi1 and miR-137 and its potential impact on neurogenesis and glioblastoma development', RNA, vol. 27, no. 5, pp. 768-782. https://doi.org/10.1261/rna.069211.118
Velasco, Mitzli X. ; Kosti, Adam ; Guardia, Gabriela D.A. ; Santos, Marcia C. ; Tegge, Allison ; Qiao, Mei ; Correa, Bruna R.S. ; Hernández, Greco ; Cearley, Erzsebet K ; Galante, Pedro A.F. ; Penalva, Luiz O. / Antagonism between the RNA-binding protein Musashi1 and miR-137 and its potential impact on neurogenesis and glioblastoma development. In: RNA. 2019 ; Vol. 27, No. 5. pp. 768-782.
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