Functional genomics analyses of RNA-binding proteins reveal the splicing regulator SNRPB as an oncogenic candidate in glioblastoma.
Glioblastoma (GBM) is the most common and aggressive type of brain tumor. Currently, GBM has an extremely poor outcome and there is no effective treatment. In this context, genomic and transcriptomic analyses have become important tools to identify new avenues for therapies. RNA-binding proteins (RBPs) are master regulators of co- and post-transcriptional events; however, their role in GBM remains poorly understood. To further our knowledge of novel regulatory pathways that could contribute to gliomagenesis, we have conducted a systematic study of RBPs in GBM.



By measuring expression levels of 1542 human RBPs in GBM samples and glioma stem cell samples, we identified 58 consistently upregulated RBPs. Survival analysis revealed that increased expression of 21 RBPs was also associated with a poor prognosis. To assess the functional impact of those RBPs, we modulated their expression in GBM cell lines and performed viability, proliferation, and apoptosis assays. Combined results revealed a prominent oncogenic candidate, SNRPB, which encodes core spliceosome machinery components. To reveal the impact of SNRPB on splicing and gene expression, we performed its knockdown in a GBM cell line followed by RNA sequencing. We found that the affected genes were involved in RNA processing, DNA repair, and chromatin remodeling. Additionally, genes and pathways already associated with gliomagenesis, as well as a set of general cancer genes, also presented with splicing and expression alterations.



Our study provides new insights into how RBPs, and specifically SNRPB, regulate gene expression and directly impact GBM development.
Centro de Oncologia Molecular, Hospital Sírio-Libanês, São Paulo, Brazil.|Children's Cancer Research Institute, UTHSCSA, San Antonio, TX, USA.
Bruna R
BR
Correa
Children's Cancer Research Institute, UTHSCSA, San Antonio, TX, USA.
Patricia Rosa
PR
de Araujo
Children's Cancer Research Institute, UTHSCSA, San Antonio, TX, USA.
Mei
M
Qiao
Children's Cancer Research Institute, UTHSCSA, San Antonio, TX, USA.
Suzanne C
SC
Burns
Georgetown University Medical Center, Washington, DC, USA.
Chen
C
Chen
Georgetown University Medical Center, Washington, DC, USA.
Richard
R
Schlegel
Georgetown University Medical Center, Washington, DC, USA.
Seema
S
Agarwal
Centro de Oncologia Molecular, Hospital Sírio-Libanês, São Paulo, Brazil. pgalante@mochsl.org.br.
Pedro A F
PA
Galante
Children's Cancer Research Institute, UTHSCSA, San Antonio, TX, USA. penalva@uthscsa.edu.|Department of Cellular and Structural Biology, UTHSCSA, San Antonio, TX, USA. penalva@uthscsa.edu.
Luiz O F
LO
Penalva
D017209:Apoptosis / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D005091:Exons; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D023281:Genomics / Q000379:methods; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D006801:Humans; D007438:Introns; D058977:Molecular Sequence Annotation; D060787:Neoplasm Grading; D011379:Prognosis; D012326:RNA Splicing / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome; D055517:snRNP Core Proteins / Q000235:genetics* / Q000378:metabolism
D016601:RNA-Binding Proteins; C526407:SNRPB protein, human; D055517:snRNP Core Proteins
Glioblastoma; Glioma stem cells; RNA-binding proteins; SNRPB; Splicing