PXD035182

PXD035182 is an original dataset announced via ProteomeXchange.

Title	SAMHD1 controls innate immunity by regulating condensation of immunogenic self RNA
Description	Recognition of pathogen-derived foreign nucleic acids is central to innate immune defense. This requires discrimination between structurally highly similar self and nonself nucleic acids to avoid aberrant inflammatory responses as in the autoinflammatory disorder Aicardi-Goutires syndrome (AGS). How vast amounts of self RNA are shielded from immune recognition to prevent autoinflammation is not fully understood. Here we show that SAM domain and HD domain-containing protein 1 (SAMHD1), one of the AGS-causing genes, functions as a single-stranded RNA (ssRNA) 3«exonuclease, the lack of which causes cellular RNA accumulation. Increased ssRNA in cells leads to dissolution of RNA-protein condensates, which sequester immunogenic double-stranded RNA (dsRNA). Release of sequestered dsRNA from condensates triggers activation of antiviral type I interferon via retinoic acid-inducible gene I-like receptors. Our results establish SAMHD1 as a key regulator of cellular RNA homeostasis and demonstrate that buffering of immunogenic self RNA by condensates regulates innate immune responses.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:23:30.299.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marc Gentzel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-08 03:36:46	ID requested
1	2023-02-06 08:19:25	announced
⏵ 2	2023-11-14 08:23:37	announced	2023-11-14: Updated project metadata.

Maharana S, Kretschmer S, Hunger S, Yan X, Kuster D, Traikov S, Zillinger T, Gentzel M, Elangovan S, Dasgupta P, Chappidi N, Lucas N, Maser KI, Maatz H, Rapp A, Marchand V, Chang YT, Motorin Y, Hubner N, Hartmann G, Hyman AA, Alberti S, Lee-Kirsch MA, SAMHD1 controls innate immunity by regulating condensation of immunogenic self RNA. Mol Cell, 82(19):3712-3728.e10(2022) [pubmed]

submitter keyword: innate immunity, human, Aicardi-Goutires syndrome (AGS),SAMHD1

Prof. Dr. Min Ae Lee-Kirsch
contact affiliation	Department of Pediatrics Medizinische Fakultät Carl Gustav Carus Technische Universität Dresden 01307 Dresden, Germany
contact email	MinAe.Lee-Kirsch@uniklinikum-dresden.de
lab head
Marc Gentzel
contact affiliation	Molecular Analysis - Mass Spectrometry, Center for Molecular and Cellular Bioengineering (CMCB), TU Dresden
contact email	marc.gentzel@tu-dresden.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/02/PXD035182

PRIDE project URI

• PRIDE
  1. PXD035182
     1. Label: PRIDE project
     2. Name: SAMHD1 controls innate immunity by regulating condensation of immunogenic self RNA