Department of Virology, Immunology, and Microbiology, Chobanian and Avedisian School of Medicine, Boston University, Boston, Massachusetts, USA.
National Emerging Infectious Diseases Laboratories, Boston University, Boston, Massachusetts, USA.
J Infect Dis. 2023 Nov 13;228(Suppl 7):S488-S497. doi: 10.1093/infdis/jiad312.
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.
埃博拉病毒(EBOV)mRNA 的 3' 非翻译区(UTR)富含 AU 含量,因此代表了针对富含 AU 元件的 RNA 结合蛋白(ARE-BP)的潜在靶标。已知 ARE-BP 可微调 RNA 周转和翻译活性。我们在 EBOV mRNA 3'UTR 内鉴定了推定的 ARE,并评估了它们是否可能调节 mRNA 稳定性。使用哺乳动物和斑马鱼胚胎报告基因测定,我们显示了一种保守的、受 ARE-BP 介导的稳定作用,以及随着测试的 EBOV 3'UTR 的增加报告基因活性。当与主要使其靶标 mRNA 不稳定的原型 ARE-BP 三肽重复蛋白(TTP,ZFP36)共表达时,EBOV 核蛋白(NP)3'UTR 导致报告基因活性降低。NP 与 TTP 共表达导致 NP 蛋白表达减少和 EBOV 小基因组活性降低。总之,EBOV 3'UTR 中 AU 残基的富集使其成为细胞 ARE-BP 的可能靶标,从而调节 RNA 稳定性和翻译活性。