Long 3'UTRs predispose neurons to inflammation by promoting immunostimulatory double-stranded RNA formation.


Journal

Science immunology
ISSN: 2470-9468
Titre abrégé: Sci Immunol
Pays: United States
ID NLM: 101688624

Informations de publication

Date de publication:
27 10 2023
Historique:
medline: 1 11 2023
pubmed: 20 10 2023
entrez: 20 10 2023
Statut: ppublish

Résumé

Loss of RNA homeostasis underlies numerous neurodegenerative and neuroinflammatory diseases. However, the molecular mechanisms that trigger neuroinflammation are poorly understood. Viral double-stranded RNA (dsRNA) triggers innate immune responses when sensed by host pattern recognition receptors (PRRs) present in all cell types. Here, we report that human neurons intrinsically carry exceptionally high levels of immunostimulatory dsRNAs and identify long 3'UTRs as giving rise to neuronal dsRNA structures. We found that the neuron-enriched ELAVL family of genes (

Identifiants

pubmed: 37862432
doi: 10.1126/sciimmunol.adg2979
doi:

Substances chimiques

3' Untranslated Regions 0
RNA, Double-Stranded 0
Receptors, Pattern Recognition 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

eadg2979

Subventions

Organisme : NINDS NIH HHS
ID : R01 NS127802
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS116141
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI171827
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM150778
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI106711
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM145440
Pays : United States

Auteurs

Tyler J Dorrity (TJ)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.

Heegwon Shin (H)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.

Kenenni A Wiegand (KA)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.

Justin Aruda (J)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.

Michael Closser (M)

Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.
Department of Neuroscience and Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Center for Motor Neuron Biology and Disease, Columbia University Irving Medical Center, New York, NY, USA.

Emily Jung (E)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.

Jake A Gertie (JA)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.
Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
Medical Scientist Training Program, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.

Amanda Leone (A)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.

Rachel Polfer (R)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.

Bruce Culbertson (B)

Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
Medical Scientist Training Program, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.

Lisa Yu (L)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.

Christine Wu (C)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.

Takamasa Ito (T)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.

Yuefeng Huang (Y)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.

Anna-Lena Steckelberg (AL)

Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.

Hynek Wichterle (H)

Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.
Department of Neuroscience and Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Center for Motor Neuron Biology and Disease, Columbia University Irving Medical Center, New York, NY, USA.

Hachung Chung (H)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.

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Classifications MeSH