Similar Datasets
Project description:The RNA exosome is a ten-subunit complex that mediates both RNA processing and degradation. This complex is evolutionarily conserved, ubiquitously expressed, and required for fundamental cellular functions, including rRNA processing. The RNA exosome plays many roles in regulating gene expression and protecting the genome, including modulating the accumulation of R-loops at sites of transcription. The RNA exosome interacts with specific target RNAs for decay or processing by interacting proteins termed cofactors. Attributing to the essential function of the RNA exosome for processes critical in all cells, such as production of mature rRNA, missense mutations in structural subunit genes of this complex cause neurological diseases. One possibility for why point mutations cause neurological diseases is that the RNA exosome partners with cell- or tissue-specific protein cofactors. Here, we employed a murine neuronal cell line (N2A) and performed immunoprecipitation of the RNA exosome subunit, EXOSC3, followed by mass spectrometry to obtain a snapshot of the RNA exosome interactome. We validated an interaction with DDX1, a putative RNA helicase. DDX1 plays roles in double-strand break repair, rRNA processing, and RNA metabolism. To explore shared functions of EXOSC3 and DDX1, we investigated the interaction after inducing DNA damage, and performed DNA/RNA immunoprecipitation followed by sequencing (DRIP-Seq) and RNA-seq on N2A cells depleted of either EXOSC3 or DDX1. These findings suggest that EXOSC3 and DDX1 function together in the absence of severe DNA damage to modulate spontaneous events such as RNA-DNA hybrid (R-loop) formation.
2024-02-12 | GSE230120 | GEO
Project description:The RNA exosome is a ten-subunit complex that mediates both RNA processing and degradation. This complex is evolutionarily conserved, ubiquitously expressed, and required for fundamental cellular functions, including rRNA processing. The RNA exosome plays many roles in regulating gene expression and protecting the genome, including modulating the accumulation of R-loops at sites of transcription. The RNA exosome interacts with specific target RNAs for decay or processing by interacting proteins termed cofactors. Attributing to the essential function of the RNA exosome for processes critical in all cells, such as production of mature rRNA, missense mutations in structural subunit genes of this complex cause neurological diseases. One possibility for why point mutations cause neurological diseases is that the RNA exosome partners with cell- or tissue-specific protein cofactors. Here, we employed a murine neuronal cell line (N2A) and performed immunoprecipitation of the RNA exosome subunit, EXOSC3, followed by mass spectrometry to obtain a snapshot of the RNA exosome interactome. We validated an interaction with DDX1, a putative RNA helicase. DDX1 plays roles in double-strand break repair, rRNA processing, and RNA metabolism. To explore shared functions of EXOSC3 and DDX1, we investigated the interaction after inducing DNA damage, and performed DNA/RNA immunoprecipitation followed by sequencing (DRIP-Seq) and RNA-seq on N2A cells depleted of either EXOSC3 or DDX1. These findings suggest that EXOSC3 and DDX1 function together in the absence of severe DNA damage to modulate spontaneous events such as RNA-DNA hybrid (R-loop) formation.
2024-02-12 | GSE230115 | GEO
Project description:The RNA helicase DDX1 associates with the nuclear RNA exosome and modulates R-loops
| PRJNA957682 | ENA
Project description:The RNA helicase DDX1 associates with the nuclear RNA exosome and modulates R-loops [RNA-seq]
| PRJNA957691 | ENA
Project description:The RNA helicase DDX1 associates with the nuclear RNA exosome and modulates R-loops [DRIP-seq]
| PRJNA957690 | ENA
Project description:Class switch recombination (CSR) at the immunoglobulin heavy-chain (IgH) locus is associated with the formation of R-loop structures over switch (S) regions. While these often occur co-transcriptionally between nascent RNA and template DNA, we now show that they also form as part of a post-transcriptional mechanism targeting AID to IgH S-regions. This depends on the RNA helicase DDX1 that is also required for CSR in vivo. DDX1 binds to G-quadruplex (G4) structures present in intronic switch transcripts and converts them into S-region R-loops. This in turn targets the cytidine deaminase enzyme AID to S-regions so promoting CSR. Notably R-loop levels over S-regions are diminished by chemical stabilization of G4 RNA or by the expression of a DDX1 ATPase-deficient mutant that acts as a dominant-negative protein to reduce CSR efficiency. In effect, we provide evidence for how S-region transcripts interconvert between G4 and R-loop structures to promote CSR in the IgH locus.
| S-EPMC5971202 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-08-12 | GSE75587 | GEO
Project description:DDX3X is a mammalian RNA helicase that regulates RNA metabolism, cancers, innate immunity and several RNA viruses. We discovered that herpes simplex virus 1, a nuclear DNA replicating virus, redirects DDX3X to the nuclear envelope where it surprisingly modulates the exit of newly assembled viral particles. DDX3X depletion also leads to an accumulation of virions in intranuclear herniations. Mechanistically, we show that DDX3X physically and functionally interacts with the virally encoded nuclear egress complex at the inner nuclear membrane. DDX3X also binds to and stimulates the incorporation in mature particles of pUs3, a herpes kinase that promotes viral nuclear release across the outer nuclear membrane. Overall, the data highlights two unexpected roles for an RNA helicase during the passage of herpes simplex viral particles through the nuclear envelope. This reveals a highly complex interaction between DDX3X and viruses and provides new opportunities to target viral propagation.
| S-EPMC9892522 | biostudies-literature
Project description:The DEAD-box RNA helicase (DDX) family plays a critical role in the growth and development of multiple organisms. DDX1 is involved in mRNA/rRNA processing and mature, virus replication and transcription, hormone metabolism, tumorigenesis, and tumor development. However, how DDX1 functions in various cancers remains unclear. Here, we explored the potential oncogenic roles of DDX1 across 33 tumors with The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. DDX1 is highly expressed in breast cancer (BRCA), cholangiocarcinoma (CHOL), and colon adenocarcinoma (COAD), but it is lowly expressed in renal cancers, including kidney renal clear cell carcinoma (KIRC), kidney chromophobe (KICH), and kidney renal papillary cell carcinoma (KIRP). Low expression of DDX1 in KIRC is correlated with a good prognosis of overall survival (OS) and disease-free survival (DFS). Highly expressed DDX1 is linked to a poor prognosis of OS for adrenocortical carcinoma (ACC), bladder urothelial carcinoma (BLCA), KICH, and liver hepatocellular carcinoma (LIHC). Also, the residue Ser481 of DDX1 had an enhanced phosphorylation level in BRCA and ovarian cancer (OV) but decreased in KIRC. Immune infiltration analysis exhibited that DDX1 expression affected CD8+ T cells, and it was significantly associated with MSI (microsatellite instability), TMB (tumor mutational burden), and ICT (immune checkpoint blockade therapy) in tumors. In addition, the depletion of DDX1 dramatically affected the cell viability of human tumor-derived cell lines. DDX1 could affect the DNA repair pathway and the RNA transport/DNA replication processes during tumorigenesis by analyzing the CancerSEA database. Thus, our pan-cancer analysis revealed that DDX1 had complicated impacts on different cancers and might act as a prognostic marker for cancers such as renal cancer.Supplementary informationThe online version contains supplementary material available at 10.1007/s43657-021-00034-x.
| S-EPMC9590584 | biostudies-literature
Project description:The RNA-degrading exosome mediates the processing and decay of many cellular transcripts. In the yeast nucleus, the ubiquitous 10-subunit exosome core complex (Exo-9-Rrp44) functions with four conserved cofactors (Rrp6, Rrp47, Mtr4, and Mpp6). Biochemical and structural studies to date have shed insights into the mechanisms of the exosome core and its nuclear cofactors, with the exception of Mpp6. We report the 3.2-Å resolution crystal structure of a S. cerevisiae Exo-9-Mpp6 complex, revealing how linear motifs in the Mpp6 middle domain bind Rrp40 via evolutionary conserved residues. In particular, Mpp6 binds near a tryptophan residue of Rrp40 that is mutated in human patients suffering from pontocerebellar hypoplasia. Using biochemical assays, we show that Mpp6 is required for the ability of Mtr4 to extend the trajectory of an RNA entering the exosome core, suggesting that it promotes the channeling of substrates from the nuclear helicase to the processive RNase.
| S-EPMC5603729 | biostudies-literature