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  • Oxford University Press (OUP)  (2)
  • 1
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), ( 2023-08-08)
    Abstract: The 3′ untranslated regions (UTRs) of Ebola virus (EBOV) mRNAs are enriched in their AU content and as such represent potential targets for RNA binding proteins targeting AU-rich elements (ARE-BPs). ARE-BPs are known to fine-tune RNA stability and translational activity, particularly of transiently expressed genes. We identified putative AREs within the 3′ UTRs of EBOV nucleoprotein mRNAs and aimed to determine whether these regions are involved in modulating EBOV mRNA post-transcriptional stability as functional targets of ARE-BPs. Using reporter assays designed to study the function of 3′ UTRs in mammalian cells and zebrafish embryos, we show that the tested EBOV 3′ UTRs increase reporter activity, either through enhancing the stability or promoting the translation of reporter mRNA, and that this stabilizing effect is conserved across species. This effect was most pronounced for the nucleoprotein (NP) 3′ UTR. When the EBOV 3′ UTR reporter constructs were co-expressed with tristetraprolin (TTP, ZFP36), a prototypic ARE-BP that is known to mainly destabilize its target mRNAs, only the NP 3′ UTR was responsive as shown by a decrease in reporter gene activity. Co-expression of EBOV NP with TTP led to downregulation of NP protein expression and reduced EBOV minigenome activity, which was dependent on the presence of the NP 3′ UTR, indicating that TTP recognizes cis-acting elements within the NP 3′ UTR. In conclusion, the enrichment of AU residues in EBOV 3′ UTRs makes them possible targets for cellular ARE-BPs, leading to modulation of RNA stability and translational activity.
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1473843-0
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  • 2
    In: PNAS Nexus, Oxford University Press (OUP)
    Abstract: Minor intron-containing genes (MIGs) account for less than 2% of all human protein coding genes and are uniquely dependent on the minor spliceosome for proper excision. Despite their low numbers, we surprisingly found significant enrichment of MIG-encoded proteins (MIG-Ps) in protein-protein interactomes and host factors of positive sense RNA viruses including, SARS-CoV-1, SARS-CoV-2, MERS-CoV, and Zika virus. Similarly, we observed significant enrichment of MIG-Ps in the interactomes and sets of host factors of negative sense RNA viruses such as Ebola virus, influenza A virus, and the retrovirus HIV-1. We also found enrichment of MIG-Ps in double stranded DNA viruses such as Epstein-Barr virus, human papillomavirus and herpes simplex viruses. In general, MIG-Ps were highly connected and placed in central positions in a network of human host protein interactions. Moreover, MIG-Ps that interact with viral proteins were enriched with essential genes. We also provide evidence that viral proteins interact with ancestral MIGs, that date back to unicellular organisms and are mainly involved in basic cellular functions, such as cell cycle, cell division, and signal transduction. Our results suggest that MIG-Ps form a stable, evolutionarily conserved backbone that viruses putatively tap to invade and propagate in human host cells.
    Type of Medium: Online Resource
    ISSN: 2752-6542
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 3120703-0
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