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J Infect Dis ; 228(Suppl 7): S488-S497, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37551415

RESUMO

The 3' untranslated regions (UTRs) of Ebola virus (EBOV) mRNAs are enriched in their AU content and therefore represent potential targets for RNA binding proteins targeting AU-rich elements (ARE-BPs). ARE-BPs are known to fine-tune RNA turnover and translational activity. We identified putative AREs within EBOV mRNA 3' UTRs and assessed whether they might modulate mRNA stability. Using mammalian and zebrafish embryo reporter assays, we show a conserved, ARE-BP-mediated stabilizing effect and increased reporter activity with the tested EBOV 3' UTRs. When coexpressed with the prototypic ARE-BP tristetraprolin (TTP, ZFP36) that mainly destabilizes its target mRNAs, the EBOV nucleoprotein (NP) 3' UTR resulted in decreased reporter gene activity. Coexpression of NP with TTP led to reduced NP protein expression and diminished EBOV minigenome activity. 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.


Assuntos
Ebolavirus , Doença pelo Vírus Ebola , Animais , Regiões 3' não Traduzidas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ebolavirus/genética , Ebolavirus/metabolismo , Doença pelo Vírus Ebola/genética , Peixe-Zebra/metabolismo , Estabilidade de RNA/genética , Mamíferos
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