PXD008364

PXD008364 is an original dataset announced via ProteomeXchange.

Title	The RIG-I like receptor LGP2 inhibits Dicer-dependent processing of long double-stranded RNA and blocks RNA interference in mammalian cells.
Description	In vertebrates, the presence of viral RNA in the cytosol is sensed by members of the RIG-I like receptor (RLR) family , which signal to induce production of type I interferons (IFN). These key anti-viral cytokines act in a paracrine and autocrine manner to induce hundreds of interferon-stimulated genes (ISGs), whose protein products restrict viral entry, replication and budding. ISGs include the RLRs themselves: RIG-I, MDA5 and the least-studied family member, LGP2. In contrast, the IFN system is absent in plants and invertebrates, which defend themselves from viral intruders using RNA interference (RNAi). In RNAi, the endoribonuclease Dicer cleaves virus-derived double stranded RNA (dsRNA) into small interfering RNAs (siRNAs) that target complementary viral RNA for cleavage. Interestingly, the RNAi machinery is conserved in mammals and we have recently demonstrated that it is able to participate in mammalian antiviral defence in conditions in which the IFN system is suppressed. In contrast, when the IFN system is active, one or more ISGs act to mask or suppress antiviral RNAi. Here, we demonstrate that LGP2 constitutes one of the ISGs that can inhibit antiviral RNAi in mammals. We identify Dicer as an LGP2-associated protein and show that LGP2 inhibits Dicer cleavage of dsRNA into siRNAs both in vitro and in vivo. Further, we show that in cells lacking an IFN response, ectopic expression of LGP2 interferes with RNAi-dependent suppression of gene expression. Thus, the inefficiency of RNAi as a mechanism of antiviral defence in mammalian somatic cells can be in part attributed to Dicer inhibition by LGP2 induced by type I IFNs.
HostingRepository	PRIDE
AnnounceDate	2018-01-17
AnnouncementXML	Submission_2018-01-24_08:45:00.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bram Snijders
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2017-12-05 01:53:39	ID requested
1	2018-01-17 00:21:08	announced
⏵ 2	2018-01-24 08:47:29	announced	Updated publication reference for PubMed record(s): 29351913.

van der Veen AG, Maillard PV, Schmidt JM, Lee SA, Deddouche-Grass S, Borg A, Kj, æ, r S, Snijders AP, Reis e Sousa C, The RIG-I-like receptor LGP2 inhibits Dicer-dependent processing of long double-stranded RNA and blocks RNA interference in mammalian cells. EMBO J, 37(4):(2018) [pubmed]

curator keyword: Biological

submitter keyword: human, immunobiology,viral infection

bram snijders
contact affiliation	The Francis Crick Institute
contact email	bram.snijders@crick.ac.uk
lab head
Bram Snijders
contact affiliation	The Francis Crick Institute
contact email	bram.snijders@crick.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD008364
     1. Label: PRIDE project
     2. Name: The RIG-I like receptor LGP2 inhibits Dicer-dependent processing of long double-stranded RNA and blocks RNA interference in mammalian cells.