Deep sequencing of sncRNAs reveals hallmarks and regulatory modules of the transcriptome during Parkinson's disease progression.

Humans RNA, Small Untranslated / genetics Transcriptome / genetics Parkinson Disease / diagnosis MicroRNAs / genetics High-Throughput Nucleotide Sequencing Disease Progression

Journal

Nature aging
ISSN: 2662-8465
Titre abrégé: Nat Aging
Pays: United States
ID NLM: 101773306

Informations de publication

Date de publication:
03 2021
Historique:
received: 08 10 2020
accepted: 08 02 2021
medline: 1 3 2021
pubmed: 1 3 2021
entrez: 28 4 2023
Statut: ppublish

Résumé

Noncoding RNAs have diagnostic and prognostic importance in Parkinson's disease (PD). We studied circulating small noncoding 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 hallmarks 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.

Identifiants

DOI: 10.1038/s43587-021-00042-6 PMID: 37118411
pubmed: 37118411
doi: 10.1038/s43587-021-00042-6
pii: 10.1038/s43587-021-00042-6
doi:

Substances chimiques

RNA, Small Untranslated 0
MicroRNAs 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

309-322

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc. part of Springer Nature.

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Auteurs

Fabian Kern (F)

Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.

Tobias Fehlmann (T)

Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.
ORCID: 0000-0003-1967-2918

Ivo Violich (I)

Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Eric Alsop (E)

Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA.

Elizabeth Hutchins (E)

Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA.
ORCID: 0000-0003-2543-0798

Mustafa Kahraman (M)

Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.

Nadja L Grammes (NL)

Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.

Pedro Guimarães (P)

Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.

Christina Backes (C)

Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.

Kathleen L Poston (KL)

Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.

Bradford Casey (B)

The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USA.
ORCID: 0000-0002-2623-5997

Rudi Balling (R)

Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.

Lars Geffers (L)

Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Department of Oncology, Luxembourg Institute of Health, Strassen, Luxembourg.

Rejko Krüger (R)

Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Transversal Translational Medicine, Luxembourg Institute of Health, Strassen, Luxembourg.
ORCID: 0000-0003-4258-6241

Douglas Galasko (D)

Department of Neurology, University of California, San Diego, La Jolla, CA, USA.

Brit Mollenhauer (B)

Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
Department of Neurology, Paracelsus-Elena-Klinik, Kassel, Germany.

Eckart Meese (E)

Department of Human Genetics, Saarland University, Homburg, Germany.

Tony Wyss-Coray (T)

Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
ORCID: 0000-0001-5893-0831

David W Craig (DW)

Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA.

Kendall Van Keuren-Jensen (K)

Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA.

Andreas Keller (A)

Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany. andreas.keller@ccb.uni-saarland.de.
Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. andreas.keller@ccb.uni-saarland.de.
ORCID: 0000-0002-5361-0895

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Deep sequencing of sncRNAs reveals hallmarks...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › Deep sequencing of sncRNAs reveals hallmarks...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › Deep sequencing of sncRNAs reveals hallmarks...
questionsmedicales.fr › Maladies du système nerveux › Maladies neurodégénératives › Maladie de Parkinson › Deep sequencing of sncRNAs reveals hallmarks...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › microARN › Deep sequencing of sncRNAs reveals hallmarks...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Séquençage nucléotidique à haut débit › Deep sequencing of sncRNAs reveals hallmarks...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Deep sequencing of sncRNAs reveals hallmarks...