Meta-analysis of multiple sclerosis microarray data reveals dysregulation in RNA splicing regulatory genes

Elvezia Maria Paraboschi, Giulia Cardamone, Valeria Rimoldi, Donato Gemmati, Marta Spreafico, Stefano Duga, Giulia Soldà, Rosanna Asselta

Research output: Contribution to journalArticlepeer-review


Abnormalities in RNA metabolism and alternative splicing (AS) are emerging as important players in complex disease phenotypes. In particular, accumulating evidence suggests the existence of pathogenic links between multiple sclerosis (MS) and altered AS, including functional studies showing that an imbalance in alternatively-spliced isoforms may contribute to disease etiology. Here, we tested whether the altered expression of AS-related genes represents a MS-specific signature. A comprehensive comparative analysis of gene expression profiles of publicly-available microarray datasets (190 MS cases, 182 controls), followed by gene-ontology enrichment analysis, highlighted a significant enrichment for differentially-expressed genes involved in RNA metabolism/AS. In detail, a total of 17 genes were found to be differentially expressed in MS in multiple datasets, with CELF1 being dysregulated in five out of seven studies. We confirmed CELF1 downregulation in MS (p = 0.0015) by real-time RT-PCRs on RNA extracted from blood cells of 30 cases and 30 controls. As a proof of concept, we experimentally verified the unbalance in alternatively-spliced isoforms in MS of the NFAT5 gene, a putative CELF1 target. In conclusion, for the first time we provide evidence of a consistent dysregulation of splicing-related genes in MS and we discuss its possible implications in modulating specific AS events in MS susceptibility genes.

Original languageEnglish
Pages (from-to)23463-23481
Number of pages19
JournalInternational Journal of Molecular Sciences
Issue number10
Publication statusPublished - Sept 30 2015


  • Alternative splicing
  • Autoimmune neurodegenerative disorder
  • Microarray
  • Multiple sclerosis
  • Peripheral blood mononuclear cells

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications


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