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

Abstract

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.

• Authors: Galina Yurevna Zheleznyakova, Eliane Piket, Maria Needhamsen, Michael Hagemann-Jensen, Diana Ekman, Yanan Han, Tojo James, Mohsen Khademi, Faiez Al Nimer, Patrick Scicluna, Jesse Huang, Ingrid Kockum, Omid R Faridani, Tomas Olsson, Fredrik Piehl, Maja Jagodic
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 118 Issue 17 (04 27 2021) ISSN: 1091-6490 [Electronic] United States
• PMID: 33879606 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 the Author(s). Published by PNAS.

Chemical References

• MicroRNAs
• RNA, Small Untranslated

Topics

• Adult
• Female
• Gene Expression (genetics)
• Gene Expression Profiling (methods)
• Humans
• Leukocytes (metabolism)
• Leukocytes, Mononuclear (metabolism)
• Male
• MicroRNAs (blood, cerebrospinal fluid, genetics)
• Middle Aged
• Multiple Sclerosis (genetics, immunology, metabolism)
• Multiple Sclerosis, Chronic Progressive (genetics)
• Multiple Sclerosis, Relapsing-Remitting (genetics)
• Neoplasm Recurrence, Local (metabolism)
• RNA, Small Untranslated (blood, cerebrospinal fluid, genetics)
• Transcriptome (genetics)