Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Caspase-mediated processing of TRBP regulates apoptosis during viral infection

ABSTRACT: RNA silencing is a post-transcriptional gene-silencing mechanism mediated by microRNAs (miRNAs). However, the regulatory mechanism of RNA silencing during viral infection is unclear. TAR RNA-binding protein (TRBP) is an enhancer of RNA silencing that induces miRNA maturation by interacting with the ribonuclease Dicer. TRBP interacts with a virus sensor protein, laboratory of genetics and physiology 2 (LGP2), in the early stage of viral infection of human cells. Next, it induces apoptosis by inhibiting the maturation of miRNAs, thereby upregulating the expression of apoptosis regulatory genes. In this study, we show that TRBP undergoes a functional conversion in the late stage of viral infection. Viral infection resulted in the activation of caspases that proteolytically processed TRBP into two fragments. The N-terminal fragment did not interact with Dicer but interacted with type I interferon (IFN) signaling modulators, such as protein kinase R (PKR) and LGP2, and induced ER stress. The end results were irreversible apoptosis and suppression of IFN signaling. Our results demonstrate that the processing of TRBP enhances apoptosis, reducing IFN signaling during viral infection.

ORGANISM(S): Homo sapiens

PROVIDER: GSE234549 | GEO | 2024/04/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Caspase-mediated processing of TRBP regulates apoptosis during viral infection

Project description:RNA silencing is a post-transcriptional gene-silencing mechanism mediated by microRNAs (miRNAs). However, the regulatory mechanism of RNA silencing during viral infection is unclear. TAR RNA-binding protein (TRBP) is an enhancer of RNA silencing that induces miRNA maturation by interacting with the ribonuclease Dicer. TRBP interacts with a virus sensor protein, laboratory of genetics and physiology 2 (LGP2), in the early stage of viral infection of human cells. Next, it induces apoptosis by inhibiting the maturation of miRNAs, thereby upregulating the expression of apoptosis regulatory genes. In this study, we show that TRBP undergoes a functional conversion in the late stage of viral infection. Viral infection resulted in the activation of caspases that proteolytically processed TRBP into two fragments. The N-terminal fragment did not interact with Dicer but interacted with type I interferon (IFN) signaling modulators, such as protein kinase R (PKR) and LGP2, and induced ER stress. The end results were irreversible apoptosis and suppression of IFN signaling. Our results demonstrate that the processing of TRBP enhances apoptosis, reducing IFN signaling during viral infection.

2024-04-19 | GSE234547 | GEO

The RIG-I like receptor LGP2 inhibits Dicer-dependent processing of long double-stranded RNA and blocks RNA interference in mammalian cells.

Project 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.

2018-01-17 | PXD008364 | Pride

LGP2 virus sensor enhances apoptosis by upregulating apoptosis-regulatory genes through TRBP-bound miRNAs during viral infection

Project description:LGP2 virus sensor enhances apoptosis by upregulating apoptosis-regulatory genes through TRBP-bound miRNAs during viral infection

| PRJNA559265 | ENA

Deletion of human tarbp2 reveals cellular microRNA targets and cell cycle function of TRBP

Project description:TRBP has two known functions as Dicer co-factor and PKR inhibitor. However, the role of TRBP in miRNA biogenesis is controversial and its regulation of PKR in mitosis remains unexplored. Here, we generate TRBP KO HeLa cells and find that TRBP depletion alters Dicer processing sites of a subset of miRNAs, but does not affect Dicer stability, miRNA abundance, or Argonaute loading. By generating PACT, another Dicer interactor, and TRBP/PACT double-KO cells, we further show that TRBP and PACT do not functionally compensate each other and that only TRBP contributes to Dicer processing. We also report that TRBP is hyperphosphorylated by JNK in M phase when PKR is activated by cellular dsRNAs. Hyperphosphorylation potentiates the inhibitory activity of TRBP on PKR, suppressing PKR in M-G1 transition. By generating the first human TRBP KO, our study clarifies the role of TRBP and unveils negative feedback regulation of PKR through TRBP phosphorylation.

2014-09-16 | GSE61458 | GEO

Deletion of human tarbp2 reveals cellular microRNA targets and cell cycle function of TRBP

2014-09-16 | E-GEOD-61458 | biostudies-arrayexpress

Caspase-mediated processing of TRBP regulates apoptosis during viral infection

Project description:Caspase-mediated processing of TRBP regulates apoptosis during viral infection

| PRJNA982025 | ENA

Caspase-mediated processing of TRBP regulates apoptosis during viral infection

Project description:Caspase-mediated processing of TRBP regulates apoptosis during viral infection

| PRJNA982032 | ENA

Caspase-mediated processing of TRBP regulates apoptosis during viral infection

Project description:Caspase-mediated processing of TRBP regulates apoptosis during viral infection

| PRJNA982029 | ENA

Human DICER helicase domain recruits PKR and dsRNA binding proteins during viral infection

Project description:The innate immune response against viruses mainly involves type I interferon (IFN) in mammalian cells. The exact contribution of the RNA silencing machinery remains to be established, but several recent studies indicate that the type III ribonuclease DICER can generate viral siRNAs in specific conditions. In addition, it has been proposed that type I IFN and RNA silencing could be mutually exclusive responses. In order to decipher the implication of DICER during infection of human cells with the Sindbis virus, we determined its interactome by immunoprecipitation and mass spectrometry analysis. Our results show that human DICER specifically interacts with several double-stranded RNA binding proteins and helicases during viral infection. In particular, proteins such as DHX9, ADAR-1 and the protein kinase PKR are enriched with DICER in virus-infected cells. We validated the importance of the helicase domain of DICER in its interaction with PKR and showed that it has functional consequences for the cellular response to viral infection.

2021-04-15 | PXD019093 | Pride

LGP2 virus sensor enhances apoptosis by upregulating apoptosis-regulatory genes through TRBP-bound miRNAs during viral infection

Project description:To reveal the fuction of cytoplasmic virus sensor protein, LGP2, on RNA silencing, we analyzed gene expression profiles on HeLa WT and LGP2 knockout cells during SeV infection, which were generated with CRISPR/Cas system.

2019-11-20 | GSE135547 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data