Department of Cellular and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Department of Biochemistry and Immunology, Ribeirão Preto Medical School, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Front Cell Infect Microbiol. 2021 Oct 19;11:718028. doi: 10.3389/fcimb.2021.718028. eCollection 2021.
Host manipulation is a common strategy for invading pathogens. , the causative agent of Chagas Disease, lives intracellularly within host cells. During infection, parasite-associated modifications occur to the host cell metabolism and morphology. However, little is known about the effect of infection on the host cell nucleus and nuclear functionality. Here, we show that can modulate host transcription and splicing machinery in non-professional phagocytic cells during infection. We found that regulates host RNA polymerase II (RNAPII) in a time-dependent manner, resulting in a drastic decrease in RNAPII activity. Furthermore, host cell ribonucleoproteins associated with mRNA transcription (hnRNPA1 and AB2) are downregulated concurrently. We reasoned that may hijack the host U2AF35 auxiliary factor, a key regulator for RNA processing, as a strategy to affect the splicing machinery activities directly. In support of our hypothesis, we carried out splicing assays using an adenovirus E1A pre-mRNA splicing reporter, showing that intracellular directly modulates the host cells by appropriating U2AF35. For the first time, our results provide evidence of a complex and intimate molecular relationship between and the host cell nucleus during infection.
宿主操纵是入侵病原体的常见策略。恰加斯病的病原体，生活在宿主细胞内。在感染过程中，寄生虫相关的改变发生在宿主细胞的代谢和形态上。然而，对于 感染对宿主细胞核和核功能的影响知之甚少。在这里，我们表明 在感染过程中非专业吞噬细胞中可以调节宿主转录和剪接机制。我们发现 可以在时间上调节宿主 RNA 聚合酶 II（RNAPII），导致 RNAPII 活性急剧下降。此外，与 mRNA 转录相关的宿主核糖核蛋白（hnRNPA1 和 AB2）也同时下调。我们推测 可能劫持宿主 U2AF35 辅助因子，一种关键的 RNA 加工调节剂，作为一种直接影响剪接机制活性的策略。为了支持我们的假设，我们使用腺病毒 E1A 前 mRNA 剪接报告基因进行了 剪接测定，表明细胞内的 直接通过利用 U2AF35 来调节宿主细胞。我们的研究结果首次提供了感染过程中 与宿主细胞核之间复杂而密切的分子关系的证据。
