4.8 Article

Small noncoding RNA profiling across cellular and biofluid compartments and their implications for multiple sclerosis immunopathology

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2011574118

Keywords

multiple sclerosis; microRNAs; small noncoding RNAs

Funding

  1. Swedish Research Council (Vetenskapsradet)
  2. Swedish Association for Persons with Neurological Disabilities
  3. Swedish Brain Foundation
  4. Swedish MS Foundation
  5. Stockholm County Council (ALF project)
  6. AstraZeneca (AstraZeneca-Science for Life Laboratory collaboration)
  7. European Union's Horizon 2020 research innovation programme [733161]
  8. European Research Council [818170]
  9. Knut and Alice Wallenberg Foundation
  10. Swedish Society for Medical Research
  11. Science for Life Laboratory
  12. Swedish National Infrastructure for Computing (SNIC)/Uppsala Multidisciplinary Center for Advanced Computational Science
  13. H2020 Societal Challenges Programme [733161] Funding Source: H2020 Societal Challenges Programme
  14. European Research Council (ERC) [818170] Funding Source: European Research Council (ERC)

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The study found widespread changes in miRNAs and other sncRNAs in patients with multiple sclerosis, especially more pronounced in CSF cells, showing a striking contrast with changes in peripheral blood cells. This suggests that sncRNA-mediated mechanisms play an important role in regulating the transcriptome of pathogenic cells, primarily in the CNS target organ.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease affecting the central nervous system (CNS). Small non-coding RNAs (sncRNAs) and, in particular, microRNAs (miRNAs) have frequently been associated with MS. Here, we performed a comprehensive analysis of all classes of sncRNAs in matching samples of peripheral blood mononuclear cells (PBMCs), plasma, cerebrospinal fluid (CSF) cells, and cell-free CSF from relapsing-remitting (RRMS, n = 12 in relapse and n = 11 in remission) patients, secondary progressive (SPMS, n = 6) MS patients, and noninflammatory and inflammatory neurological disease controls (NINDC, n = 11; INDC, n = 5). We show widespread changes in miRNAs and sncRNA-derived fragments of small nuclear, nucleolar, and transfer RNAs. In CSF cells, 133 out of 133 and 115 out of 117 differentially expressed sncRNAs were increased in RRMS relapse compared to remission and RRMS compared to NINDC, respectively. In contrast, 65 out of 67 differentially expressed PBMC sncRNAs were decreased in RRMS compared to NINDC. The striking contrast between the periphery and CNS suggests that sncRNA-mediated mechanisms, including alternative splicing, RNA degradation, and mRNA translation, regulate the transcriptome of pathogenic cells primarily in the CNS target organ.

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