ZIKV prevents host mRNA export from the nucleus by disrupting UPF1 function
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ABSTRACT:
PROVIDER: PRJNA672317 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12906040.fastq.gz | Fastqsanger.gz | |||
| SRR12906041.fastq.gz | Fastqsanger.gz | |||
| SRR12906042.fastq.gz | Fastqsanger.gz | |||
| SRR12906043.fastq.gz | Fastqsanger.gz | |||
| SRR12906044.fastq.gz | Fastqsanger.gz |
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Project description:Zika virus (ZIKV) is a mosquito-borne virus that can have dramatic neurodevelopmental consequences when infection occurs in utero. Previous studies demonstrated that ZIKV downregulates the master regulator of nonsense mediated decay, UPF1. To examine whether this process contributes to disruption of neural development, we investigated the effect of ZIKV infection on UPF1 interaction with host RNA in neural progenitor cells. Here, we show that ZIKV-mediated disruption of UPF1 function in neural progenitor cells causes retention of mRNA in the nucleus, resulting in decreased protein levels of specific transcripts involved in neural differentiation.
2022-12-22 | GSE160201 | GEO
Project description:UPF1 is an ATP-driven RNA helicase required for efficient nonsense mediated mRNA decay in eukaryotes. Although it is currently understood that UPF1 primarily acts on the 3’UTR of translating mRNAs in the cytoplasm, our data indicates that this is a highly dynamic protein that is rapidly shuttling between nucleus and cytoplasm in Drosophila. Additionally, ChIP-seq analysis in different cell types demonstrates genome-wide association of UPF1 with nascent RNAs at most of the active Pol II transcription sites, and at some specific Pol III genes. Notably, intron recognition appears to interfere with association and translocation of UPF1 on nascent transcripts. Cells depleted of UPF1 show defects in nuclear processes such as mRNA export and transcription site retention. These data, thus redefine UPF1 as a global player in mRNA based processes in the nucleus as well as the cytoplasm.
2019-04-01 | GSE116808 | GEO
Project description:ChIP with NMD core componenet UPF1 antibody in normal S2 cells and ChIP with Pol II Ser2 antibodies in S2 cells. UPF1 is an ATP-driven RNA helicase required for efficient nonsense mediated mRNA decay in eukaryotes. Although it is currently understood that UPF1 primarily acts on the 3’UTR of translating mRNAs in the cytoplasm, our data indicates that this is a highly dynamic protein that is rapidly shuttling between nucleus and cytoplasm in Drosophila. Additionally, ChIP-seq analysis in different cell types demonstrates genome-wide association of UPF1 with nascent RNAs at most of the active Pol II transcription sites, and at some specific Pol III genes. Notably, intron recognition appears to interfere with association and translocation of UPF1 on nascent transcripts. Cells depleted of UPF1 show defects in nuclear processes such as mRNA export and transcription site retention. These data, thus redefine UPF1 as a global player in mRNA based processes in the nucleus as well as the cytoplasm.
2019-04-01 | GSE116806 | GEO
Project description:Cancer-associated SF3B1 Mutations Inhibit mRNA Nuclear Export by Disrupting SF3B1–THOC5 Interactions
| PRJNA1116549 | ENA
Project description:Pre-mRNA splicing and nuclear export are coordinated processes that ensure efficient and accurate gene expression. In recent years, disruptions in this process have been found to result in substantial gene expression aberrations, with potential contributions from SF3B1 mutations, whose mechanism remains elusive. The present study reveals that the K700E mutation in SF3B1 attenuates its interaction with THOC5, resulting in reduced mRNA binding by THOC5, and ultimately, the inhibition of mRNA nuclear export. Interestingly, overexpressing THOC5 can restore the attenuated interaction, facilitating mRNA nuclear export. Importantly, other cancer-associated SF3B1 mutations may exert a similar impact. Our research highlights the critical role of the THOC5–SF3B1 interaction in regulating mRNA nuclear export and provides valuable insights into the impact of SF3B1 mutations on this process.
2024-09-12 | GSE268355 | GEO
Project description:Zika virus (ZIKV) infection causes microcephaly and has been linked to other brain abnormalities. How ZIKV impairs brain development and function remains elusive. Here we systematically profiled transcriptomes of human neural progenitor cells (hNPCs) and astrocytes exposed to Asian ZIKVC, African ZIKVM, and Dengue virus (DENV). DENV causes distinct gene expression changes; and ZIKV has a broader impact on the expression of gene involved in DNA replication and repair. While overall expression profiles are similar, ZIKVC, but not ZIKVM, induces upregulation of viral response genes. Upon ZIKV infection, astrocytes exhibit more prominent transcriptome changes than hNPCs, particularly enriching genes related to inflammatory response and cytokine production pathways. Our analyses reveal cell-type- and strain-specific molecular signatures associated with ZIKV infection, and identify astrocytes as a major direct target of ZIKV. Further investigation of ZIKV-host interactions based our transcriptomic datasets may help to illuminate neural virulence determinants of ZIKV in patients. Gene Expression Analyses of the cells infected with different flaviviruses
2016-08-23 | E-GEOD-80434 | biostudies-arrayexpress
Project description:To determine the effect of Zika virus infection on pre-implantation embryonic development, we performed single blastocyst RNA-Seq on MOCK and ZIKV infected embryos. ZIKV infection results in an increased risk of spontaneous abortion and poor intrauterine growth although the mechanisms underlying fetal loss remain undetermined. Little is known about the impact of ZIKV infection during the earliest stages of pregnancy, or pre- and peri-implantation, because most current studies of ZIKV infection in pregnancy models focus on post-implantation stages. Here, we demonstrate that trophectoderm cells of pre-implantation human and mouse embryos can be efficiently infected with ZIKV, and that trophectoderm can propagate virus causing cell death of neural progenitors. These findings were corroborated by our demonstration that hESC-derived trophectoderm cells are infected by ZIKV in a dose dependent manner. RNAseq of single blastocysts revealed key transcriptional changes in cellular and physiologic functions upon ZIKV infection, including nervous system development and function, prior to commitment to the neural cell lineage. Finally, the pregnancy rate of mice infected pre-implantation was > 50% lower than females infected at E4.5. These results demonstrate that pre-implantation ZIKV infection of trophectoderm leads to miscarriage or spontaneous abortion. Moreover, pre- and peri-implantation ZIKV infects trophectoderm cells that propagate virus over time causing cell death in neural progenitors. Cumulatively, these data demonstrate that vertical pre- and peri-implantation ZIKV infection of trophectoderm impairs fetal development and causes neural progenitor cell death, elucidating a previously unappreciated association of pre- and peri-implantation ZIKV infection and microcephaly.
2019-08-16 | GSE133254 | GEO
Project description:To identify high-confidence NMD targets in mouse N2A neuroblastoma cells, we used our established transcriptome-wide RNA sequencing (RNA-seq) methodologies. Through parallel analyses of RNA-seq upon UPF1-knockdown (KD) and RNA immunoprecipitation (RIP-seq) footprinting of p-UPF1-bound RNAs, we identified 1027 high-confidence neuronal NMD targets.
2021-10-25 | GSE180134 | GEO
Project description:DNA/RNA helicase Upf1 seems to interact with axonal transcripts in response to nerve growth factor (NGF, A. Ludanyi, M. Gaspari and A. Riccio, unpublished data). In order to shed light on Upf1 mechanism of action and to identify potential associations with molecules having cleavage activity, we performed an AP-MS experiment comprising Upf1 immunoprecipitation, on-beads digestion, isotopic labelling (18O) and quantitative LC-MS/MS analysis.
2021-09-10 | PXD023586 | Pride
Project description:Nonsense-mediated mRNA decay (NMD) controls the quality of eukaryotic gene expression and also degrades physiologic mRNAs. How NMD targets are identified is incompletely understood. A central NMD factor is the ATP-dependent RNA helicase UPF1. Neither the distance in space between the termination codon and the poly(A) tail nor the binding of steady-state, largely hypophosphorylated UPF1 is a discriminating marker of cellular NMD targets, unlike for PTC-containing reporter mRNAs when compared to their PTC-free counterparts. Here, we map phosphorylated UPF1 (p-UPF1) binding sites using transcriptome-wide footprinting or DNA oligonucleotide-directed mRNA cleavage to report that p-UPF1 provides the first reliable cellular NMD-target marker. p-UPF1 is enriched on NMD target 3'UTRs along with SMG5 and SMG7 but not SMG1 or SMG6. Immunoprecipitations of UPF1 variants deficient in various aspects of the NMD process in parallel with FRET experiments reveal that ATPase/helicase-deficient UPF1 manifests high levels of RNA binding and disregulated hyperphosphorylation, whereas wild-type UPF1 releases from nonspecific RNA interactions in an ATP hydrolysis-dependent mechanism until an NMD target is identified. 3'UTR-associated UPF1 undergoes regulated phosphorylation on NMD targets, providing a binding platform for mRNA degradative activities. p-UPF1 binding to NMD target 3'UTRs is stabilized by SMG5 and SMG7. Our results help to explain why steady-state UPF1 binding is not a marker for cellular NMD substrates and how this binding is transformed to induce mRNA decay. RIP-seq experiments for p-UPF1, control IPs using rabbit IgG and additional control sample without IP were performed in duplicates
2014-08-15 | E-GEOD-60045 | biostudies-arrayexpress