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Ubiquitination of DEAD-box RNA helicase DDX3X by TRIM25

ABSTRACT: Tripartite motif protein 25 (TRIM25) is an E3 ligase that ubiquitinates multiple substrates within the RLR signalling cascade and plays both RING (really interesting new gene)-dependent and RING-independent roles in RIG-I-mediated IFN induction. We report that the PRY-SPRY domain of TRIM25 interacts with the N-terminal extension (NTE) of DEAD-box helicase 3X (DDX3X), a host protein with multiple roles in RLR signalling. Gene reporter assays and knockdown studies reveal DDX3X and TRIM25 cooperate to activate the IFN- promoter following RIG-I activation independent of DDX3X’s catalytic activity. We also show that TRIM25 ubiquitinates DDX3X at several lysine residues in vitro and in cells.

INSTRUMENT(S): LTQ Orbitrap XL

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Oded Kleifeld

LAB HEAD: Natalie Borg

PROVIDER: PXD028122 | Pride | 2021-09-08

REPOSITORIES: Pride

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			Action	DRS
	2020-10-29-decoys-reviewed-contam-UP000005640.fas	Other
	Seq30746_E1O1.RAW	Raw
	Seq30746_E1O1.mzML	Mzml
	Seq30746_E1O1.pepXML	Pepxml
	fragger.params	Other

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Publications

TRIM25 and DEAD-Box RNA Helicase DDX3X Cooperate to Regulate RIG-I-Mediated Antiviral Immunity.

Atkinson Sarah C SC Heaton Steven M SM Audsley Michelle D MD Kleifeld Oded O Borg Natalie A NA

International journal of molecular sciences 20210823 16

The cytoplasmic retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) initiate interferon (IFN) production and antiviral gene expression in response to RNA virus infection. Consequently, RLR signalling is tightly regulated by both host and viral factors. Tripartite motif protein 25 (TRIM25) is an E3 ligase that ubiquitinates multiple substrates within the RLR signalling cascade, playing both ubiquitination-dependent and -independent roles in RIG-I-mediated IFN induction. However, addition ...[more]

PMID: 34445801

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The long noncoding RNA Lnczc3h7a promotes TRIM25-mediated RIG-I antiviral innate immune response

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Project description:The only membrane-anchored and essential ATP-dependent protease in Escherichia coli is FtsH. It controls the intracellular concentration of the deacetylase LpxC, which catalyses the first committed step in lipopolysaccharide biosynthesis. LpxC stability is strictly regulated in a growth rate-dependent manner to ascertain a vital equilibrium of lipopolysaccharide (LPS) and phospholipid biosynthesis. Previous studies suggested the involvement of yet unknown factors in LpxC degradation. Aiming at the identification of such factors that are predicted to be associated with LpxC and/or FtsH at high and low growth rates, we established a quantitative super-SILAC LC-MS/MS-based approach. The identification of known LpxC and FtsH interactors validated our approach. Several enzymes involved in fatty acid biosynthesis and degradation, including the central regulator FadR, interacted with LpxC and/or FtsH and showed a significant impact on LpxC stability. The newly identified LpxC and FtsH interactor WaaH, a LPS-modifying enzyme, stimulates LpxC degradation. Our results go beyond the previously established link between LPS and phospholipid biosynthesis and uncover a far-reaching network that controls LPS biosynthesis by involving multiple enzymes in fatty acid metabolism and phospholipid biosynthesis and modification.

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circRNA expression data from human non-small cell lung cancer tissues and the correponding non-cancerous tissues

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Project description:Both bacterial and viral diseases are a major threat to farmed fish, as well as wild fish. As the antiviral immune mechanisms in lumpfish (Cyclopterus lumpus L.) are poorly understood, lumpfish leukocytes were stimulated with poly(I:C), a synthetic analog of virus dsRNA, and RNA sequencing was performed. Immune genes were identified, and transcriptome-wide analyses of early immune responses in lumpfish leukocytes showed that 310 and 1872 transcripts were significantly differentially expressed 6 and 24 hours post exposure (hpe) to poly(I:C), respectively. The most enriched GO terms when time had been accounted for, were immune system processes (GO:0002376) and immune response (GO:0006955). Analysis of differentially expressed genes (DEGs) showed that among the most highly upregulated genes were TLRs and genes belonging to the RIG-I signaling pathway, including LGP2, MDA5, TRIM25, STING, as well as IRF3, IL-8 and TNFα. RIG-I was not identified, but in silico analyses showed that genes encoding proteins involved in pathogen recognition, cell signaling, and cytokines of the TLR and RIG-I signaling pathway are mostly conserved in lumpfish when compared to mammals and other teleost species. Our analyses unravel the innate immune pathways playing a major role in antiviral defence in lumpfish. The information gathered can be used to compare research findings and lay the groundwork for future functional analyses of immune and pathogenicity mechanisms. Such knowledge is also necessary for the development of immunoprophylactic measures for lumpfish, which is extensively cultivated for use as cleaner fish in the aquaculture for removal of sea lice from Atlantic salmon (Salmo salar).

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TRIM25

Project description:TRIM25

| PRJNA316328 | ENA

The long noncoding RNA Lnczc3h7a promotes TRIM25-mediated RIG-I antiviral innate immune response

Project description:The long noncoding RNA Lnczc3h7a promotes TRIM25-mediated RIG-I antiviral innate immune response

| PRJNA443151 | ENA

RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination

Project description:TRIM25 E3 ubiquitin ligase is a new RNA-binding protein. We present the first high-throughput analysis of the molecular interactomes of TRIM25. We show that TRIM25 is a bona fide RNA-binding protein that interacts with numerous coding and non-coding transcripts. This suggests that TRIM25 could play a role in the regulation of RNA metabolism.

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DDX3X regulation of global translation is impaired by medulloblastoma-associated mutations [RiboSeq]

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