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

Author(s):Show less -

Velasco, Mitzli X. ^{[1, 2]} ; Kosti, Adam ^{[1, 3]} ; Guardia, Gabriela D. A. ^[4] ; Santos, Marcia C. ^[1] ; Tegge, Allison ^[5] ; Qiao, Mei ^[1] ; Correa, Bruna R. S. ^{[1, 4]} ; Hernandez, Greco ^[2] ; Kokovay, Erzsebet ^[3] ; Galante, Pedro A. F. ^[4] ; Penalva, Luiz O. F. ^{[1, 3]}

Affiliation

^[1] Univ Texas Hlth Sci Ctr San Antonio, Greheey Childrens Res Inst, San Antonio, TX 78229 - USA

^[2] Natl Inst Canc INCan, Translat & Canc Lab, Unit Biomed Res Canc, Mexico City 14080, DF - Mexico

^[3] Univ Texas Hlth Sci Ctr San Antonio, Dept Cell Syst & Anat, San Antonio, TX 78229 - USA

^[4] Hosp Sirio Libanes, Ctr Oncol Mol, BR-01308050 Sao Paulo - Brazil

^[5] Virginia Tech, Dept Stat, Blacksburg, VA 14080 - USA

• Document type: Journal article
• Source: RNA; v. 25, n. 7, p. 768-782, JUL 2019.
• Web of Science Citations: 0

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). (AU)

• FAPESP's process: 13/07159-5 - RNA-binding proteins and post-transcriptional variations: influence on glioblastoma multiforme development
• Grantee: Bruna Renata Silva Corrêa
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/19541-2 - Impact of RNA binding proteins on abnormal regulation of splicing in glioblastoma
• Grantee: Gabriela Der Agopian Guardia
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/25483-4 - Identification and functional analysis of RNA binding proteins associated with the development of glioblastoma multiform
• Grantee: Bruna Renata Silva Corrêa
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate