Vaccinia virus D10 has broad decapping activity that is regulated by mRNA splicing
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ABSTRACT:
PROVIDER: PRJNA769420 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16235569_1.fastq.gz | Fastqsanger.gz | |||
| SRR16235569_2.fastq.gz | Fastqsanger.gz | |||
| SRR16235570_1.fastq.gz | Fastqsanger.gz | |||
| SRR16235570_2.fastq.gz | Fastqsanger.gz | |||
| SRR16235571_1.fastq.gz | Fastqsanger.gz |
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Project description:Vaccinia virus (VACV) encodes decapping enzyme D10 that suppresses gene expression by removing the protective 5’ cap off mRNAs, rendering them susceptible to degradation by cellular exonucleases. Here, we use RNA-seq to profile the repertoire of transcripts targeted by D10 in isolation as well as in the context of VACV infection. We found that D10 is a broadly acting decapping enzyme and targets the vast majority of human transcripts. Notably, we found that the splicing architecture of a gene influences how robustly its corresponding transcript is targeted by D10, with transcripts derived from intronless genes being less susceptible to D10 activity. Since all viral genes are intronless, and some viral transcripts are uncapped, D10 preferentially targets host transcripts over viral transcripts. The disproportionate activity of D10 towards host transcripts may help the virus restrict host innate immune response and shift the translational resources towards viral protein synthesis.
2022-02-02 | GSE185520 | GEO
Project description:The mRNA 5' cap structure serves both to protect transcripts from degradation and promote their translation. Cap removal is thus an integral component of mRNA turnover that is carried out by cellular decapping enzymes, whose activity is tightly regulated and coupled to other stages of the mRNA decay pathway. The poxvirus vaccinia virus (VACV) encodes its own decapping enzymes, D9 and D10, that act on cellular and viral mRNA, but may be regulated differently than their cellular counterparts. Here, we evaluated the targeting potential of these viral enzymes using RNA sequencing from cells infected with wild-type and decapping mutant versions of VACV as well as in uninfected cells expressing D10. We found that D9 and D10 target an overlapping subset of viral transcripts but that D10 plays a dominant role in depleting the vast majority of human transcripts, although not in an indiscriminate manner. Unexpectedly, the splicing architecture of a gene influences how robustly its corresponding transcript is targeted by D10, as transcripts derived from intronless genes are less susceptible to enzymatic decapping by D10. As all VACV genes are intronless, preferential decapping of transcripts from intron-containing genes provides an unanticipated mechanism for the virus to disproportionately deplete host transcripts and remodel the infected cell transcriptome.
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Project description:Decapping enzymes are required for the removal of the 5'-end (m7)GpppN cap of mRNAs to allow their decay in cells. While many cap-binding proteins recognize the cap structure via the stacking of the methylated guanosine ring between two aromatic residues, the precise mechanism of cap recognition by decapping enzymes has yet to be determined. In order to get insights into the interaction of decapping enzymes with the cap structure, we studied the vaccinia virus D10 decapping enzyme as a model to investigate the important features for substrate recognition by the enzyme. We demonstrate that a number of chemically modified purines can competitively inhibit the decapping reaction, highlighting the molecular features of the cap structure that are required for recognition by the enzyme, such as the nature of the moiety at positions 2 and 6 of the guanine base. A 3D structural model of the D10 protein was generated which suggests amino acids implicated in cap binding. Consequently, we expressed 17 mutant proteins with amino acid substitutions in the active site of D10 and found that eight are critical for the decapping activity. These data underscore the functional features involved in the non-canonical cap-recognition by the vaccinia virus D10 decapping enzyme.
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Project description:Through its activity in stereocilia, MYO7A (myosin VIIA) is essential for hair cell function in the inner ear. Utilizing multiple stages of immunoaffinity enrichment, we have developed a strategy that allows us to partially purify stereocilia membranes from thousands of chick inner ears and isolate low-abundance MYO7A protein complexes from those membranes. The D10 stereocilia membrane enrichment protocol involves density centrifugation steps and immuno-enrichment of stereocilia using the D10 antibody, directed against the major stereocilia transmembrane protein PTPRQ. The data in this submission document the effectiveness of the enrichment procedure.
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Project description:The Dcp2 and Nudt16 Nudix hydrolases, are mRNA decapping enzymes that preferentially modulate stability of a subset of mRNAs. Here we report Nudt3 is a third Nudix protein that possess mRNA decapping activity in cells and is a modulator of cell migration in MCF-7 breast cancer cells. Genome-wide analysis of Nudt3 compromised cells identified increases in mRNAs involved in cell motility including integrin β6, lipocalin-2 and fibronectin. The increase in mRNA levels was dependent on Nudt3 decapping activity where integrin β6 and lipocalin-2 were modulated directly through mRNA stability, while fibronectin was indirectly controlled. Moreover, increased cell migration observed in Nudt3 depleted cells was mediated through the extracellular integrin β6 and fibronectin protein nexus. We conclude, Nudt3 is an mRNA decapping enzyme that orchestrates expression of a subset of mRNAs to modulate cell migration and further substantiates the existence of multiple decapping enzymes functioning in distinct cellular pathways in mammals. Stably transformed MCF-7 cell lines constitutively expressing either a short hairpin RNA (shRNA) directed against Nudt3 (Nudt3KD) or a non-targeted control shRNA (ConKD) were used, with three replicate cultures used per group (n=3).
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Project description:Transcriptional profiling of parental S. cerevisiae San I cells in comparison with its translocant derivative D10 Small strain. The latter strain was obtained using Bridge Induced translocation technique between DUR3 gene (Chromosome VIII) and ADH1 gene (Chromosome XV), and exhibited an abnormal phenotype comprising elongated buds and multi-budded, unevenly nucleated pseudo-hyphae. Goal was to demonstrate how chromosomal translocations can influence gene expression of translocant and other chromosomes. Two-condition experiment, direct comparison of Saccharomyces cerevisiae D10 small (4 biological replicates) vs. pooled WT San I (reference) cells.
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| PRJNA238138 | ENA