Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Nat Commun. 2022 Feb 2;13(1):623. doi: 10.1038/s41467-022-28144-8.
RNA polymerase III (Pol III) transcribes noncoding RNA, including transfer RNA (tRNA), and is commonly targeted during cancer and viral infection. We find that Herpes Simplex Virus-1 (HSV-1) stimulates tRNA expression 10-fold. Perturbation of host tRNA synthesis requires nuclear viral entry, but not synthesis of specific viral transcripts. tRNA with a specific codon bias were not targeted-rather increased transcription was observed from euchromatic, actively transcribed loci. tRNA upregulation is linked to unique crosstalk between the Pol II and III transcriptional machinery. While viral infection results in depletion of Pol II on host mRNA promoters, we find that Pol II binding to tRNA loci increases. Finally, we report Pol III and associated factors bind the viral genome, which suggests a previously unrecognized role in HSV-1 gene expression. These findings provide insight into mechanisms by which HSV-1 alters the host nuclear environment, shifting key processes in favor of the pathogen.
RNA 聚合酶 III（Pol III）转录非编码 RNA，包括转移 RNA（tRNA），并且在癌症和病毒感染期间通常是靶向目标。我们发现单纯疱疹病毒-1（HSV-1）刺激 tRNA 表达增加了 10 倍。干扰宿主 tRNA 合成需要核病毒进入，但不需要合成特定的病毒转录本。具有特定密码子偏好的 tRNA 未成为目标，而是在常染色质、活跃转录的基因座观察到转录增加。tRNA 的上调与 Pol II 和 III 转录机制之间独特的串扰有关。虽然病毒感染导致宿主 mRNA 启动子上的 Pol II 耗竭，但我们发现 Pol II 结合 tRNA 基因座的增加。最后，我们报告 Pol III 和相关因子结合病毒基因组，这表明在 HSV-1 基因表达中具有以前未被认识的作用。这些发现为 HSV-1 改变宿主核环境的机制提供了深入的了解，有利于病原体的关键过程。
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