Article (Scientific journals)
Deep sequencing of sncRNAs reveals hallmarks and regulatory modules of the transcriptome during Parkinson’s disease progression
KRÜGER, Rejko; Kern, Fabian; Fehlmann, Tobias et al.
2021In Nature Aging
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Keywords :
Parkinson's disease; RNAs; PPMI
Abstract :
[en] Noncoding RNAs have diagnostic and prognostic importance in Parkinson’s disease (PD). We studied circulating small non coding RNAs (sncRNAs) in two large-scale longitudinal PD cohorts (Parkinson’s Progression Markers Initiative (PPMI) and Luxembourg Parkinson’s Study (NCER-PD)) and modeled their impact on the transcriptome. Sequencing of sncRNAs in 5,450 blood samples of 1,614 individuals in PPMI yielded 323 billion reads, most of which mapped to microRNAs but covered also other RNA classes such as piwi-interacting RNAs, ribosomal RNAs and small nucleolar RNAs. Dysregulated microRNAs associated with disease and disease progression occur in two distinct waves in the third and seventh decade of life. Originating predominantly from immune cells, they resemble a systemic inflammation response and mitochondrial dysfunction, two hall marks of PD. Profiling 1,553 samples from 1,024 individuals in the NCER-PD cohort validated biomarkers and main findings by an independent technology. Finally, network analysis of sncRNA and transcriptome sequencing from PPMI identified regulatory modules emerging in patients with progressing PD
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
KRÜGER, Rejko ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience
Kern, Fabian;  Saarland University
Fehlmann, Tobias;  Saarland University
Violich, Ivo;  University of Southern California
Hutchins, Elizabeth;  Neurogenomics Division, Translational Genomics Research Institute
Alsop, Eric;  Neurogenomics Division, Translational Genomics Research Institute
Kahraman, Mustafa;  Saarland University
Grammes, Nadja;  Saarland University
BALLING, Rudolf ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
GEFFERS, Lars ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Keller, Andreas;  Saarland University
External co-authors :
yes
Language :
English
Title :
Deep sequencing of sncRNAs reveals hallmarks and regulatory modules of the transcriptome during Parkinson’s disease progression
Publication date :
15 March 2021
Journal title :
Nature Aging
ISSN :
2662-8465
Publisher :
springer
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
FnR Project :
FNR11264123 - Ncer-pd, 2015 (01/01/2015-30/11/2020) - Rejko Krüger
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since 19 January 2022

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