Profiling of small non-coding RNAs across cellular and biofluid compartments: implications for multiple sclerosis immunopathology

Zheleznyakova, G. Y.; Piket, E.; Needhamsen, M.; Hagemann-Jensen, M.; Ekman, D.; Khademi, M.; Al Nimer, F.; Scicluna, P.; Faridani, O. R.; Olsson, T.; Piehl, F.; Jagodic, M.

doi:10.1101/2020.05.15.097519

bioRxiv · 10.1101/2020.05.15.097519

Profiling of small non-coding RNAs across cellular and biofluid compartments: implications for multiple sclerosis immunopathology

Zheleznyakova, G. Y.·Piket, E.·Needhamsen, M.·Hagemann-Jensen, M.·Ekman, D.·Khademi, M.·Al Nimer, F.·Scicluna, P.·Faridani, O. R.·Olsson, T.·Piehl, F.·Jagodic, M.

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Abstract

Multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), is associated with dysregulation of microRNAs (miRNA). We here analyzed all classes of small non-coding RNAs (sncRNAs) in matching peripheral blood mononuclear cells (PBMCs), plasma, cerebrospinal fluid (CSF) cells and cell-free CSF from relapsing-remitting (RRMS, n=12 in relapse, n=11 in remission), secondary progressive (SPMS, n=6) MS patients and non-inflammatory and inflammatory neurological disease controls (NINDC, n=11; INDC, n=5). We show widespread changes in small nuclear, nucleolar, transfer RNAs and miRNAs. In CSF cells, 133/133 and 115/117 differentially expressed sncRNAs are increased in RRMS relapse compared to remission and RRMS compared to NINDC, respectively. In contrast, 65/67 differentially expressed PBMC sncRNAs are decreased in RRMS compared to NINDC. The striking contrast between 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 target organ.

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Zheleznyakova, G. Y., Piket, E., Needhamsen, M., Hagemann-Jensen, M., Ekman, D., Khademi, M., Al Nimer, F., Scicluna, P., Faridani, O. R., Olsson, T., Piehl, F., Jagodic, M.. 2020-05-16. Profiling of small non-coding RNAs across cellular and biofluid compartments: implications for multiple sclerosis immunopathology. https://doi.org/10.1101/2020.05.15.097519

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