UUUUUNU oligonucleotide inhibition of RNA synthesis in vaccinia virus cores.
UUUUUNU oligonucleotide inhibition of RNA synthesis in vaccinia virus cores.
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UUUUUNU 寡核苷酸抑制牛痘病毒核心 RNA 合成。
DOI：
10.1016/j.virol.2004.04.003
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Niles,EdwardG
中科院分区：
文献类型：
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作者：
Mohamed,MohamedRagaa;Niles,EdwardG
该实验室的最新结果表明，含U5NU的寡核苷酸在体外刺激早期基因转录提前终止的能力。对刺激提前终止的寡核苷酸序列和结构要求的进一步研究表明，只有具有磷酸二酯键的核糖尿嘧啶U9的寡核苷酸才有活性。因为短至9个碱基的寡核苷酸作为过早转录终止的有效刺激物，我们推断短的含U5NU的寡核苷酸可能作为有效的抗痘病毒剂，因为它们会阻止全尺寸早期mRNA的合成。为了在体内有用，寡核苷酸不仅必须被感染的细胞吸收，而且还必须能够进入病毒核心，即早期基因转录的位点，并保持其刺激过早终止的能力。评价了含U9的寡核苷酸抑制病毒核心RNA合成的能力。U5NU寡核苷酸表现出显着的序列特异性抑制核心RNA的合成，与它们的能力，刺激早期基因转录的提前终止一致。此外，发现9聚体RNA比17或22聚体RNA表现出一半最大RNA合成抑制所需的U5NU寡核苷酸浓度更低。这表明较小的寡核苷酸可能更容易接近核心。这一观察结果支持了这样的寡核苷酸可以作为有效的抗痘病毒治疗剂的观点。
Recent results from this laboratory demonstrated the ability of U5NU-containing oligonucleotides to stimulate premature termination of early gene transcription in vitro. Further studies on the oligonucleotide sequence and structural requirements for stimulating premature termination demonstrated that only oligonucleotides possessing ribouracil U9 with a phosphodiester linkage are active. Because an oligonucleotide as short as 9 bases serves as an effective stimulator of premature transcription termination, we reasoned that short U5NU-containing oligonucleotides might serve as efficacious anti-poxvirus agents because they would prevent the synthesis of full-sized early mRNA. To be useful in vivo, the oligonucleotides must not only be taken up by the infected cells, but also be able to enter the virus core, the site of early gene transcription, and retain their ability to stimulate premature termination. The ability of U9-containing oligonucleotides to inhibit virus core RNA synthesis was evaluated. The U5NU oligonucleotides exhibited a dramatic sequence-specific inhibition of core RNA synthesis, consistent with their ability to stimulate premature termination of early gene transcription. Moreover, the concentration of U5NU oligonucleotide required to exhibit half maximal inhibition of RNA synthesis was found to be less for a 9 mer RNA than it was for a 17 or 22 mer RNA. This suggests the possibility that the smaller oligonucleotides may have easier access to the core. This observation lends support to the notion that such oligonucleotides might serve as effective anti-poxvirus therapeutic agents.