Bermudez Yahaira, Miles Jacob, Muller Mandy
Department of Microbiology, University of Massachusetts, Amherst, 639 North Pleasant street, Morrill IV North, MA 01003 USA.
iScience. 2023 Jan 20;26(1):105887. doi: 10.1016/j.isci.2022.105887. Epub 2022 Dec 28.
Extensive remodeling of host gene expression by nonstructural protein 1 (nsp1) of coronaviruses is a well-documented and conserved aspect of coronavirus-host takeover. Using comparative transcriptomics we investigated the diversity of transcriptional targets between various nsp1 proteins. Additionally, affinity purification followed by mass spectrometry was implemented to identify common interactors between the different nsp1 proteins. Although we detected widespread RNA destabilization, closely related nsp1 showed little similarities in clustering of targeted genes. We observed a partial overlap in transcriptional targeting between α-CoV 229E and MERS nsp1, which may suggest a common targeting mechanism, as MERS nsp1 preferentially targets nuclear transcripts. Our interactome data show great variability between nsp1 interactions, with 229E nsp1, the smallest nsp1 tested here, interacting with the most number of host proteins. Although nsp1 is a rather well-conserved protein with conserved functions across different coronaviruses, our data indicate that its precise effects on the host cell are virus specific.
冠状病毒非结构蛋白1（nsp1）对宿主基因表达的广泛重塑是冠状病毒接管宿主这一过程中一个有充分文献记载且保守的方面。我们利用比较转录组学研究了不同nsp1蛋白之间转录靶点的多样性。此外，还进行了亲和纯化后质谱分析，以鉴定不同nsp1蛋白之间的共同相互作用分子。尽管我们检测到广泛的RNA不稳定现象，但亲缘关系较近的nsp1在靶向基因聚类方面几乎没有相似之处。我们观察到α-CoV 229E和中东呼吸综合征（MERS）nsp1在转录靶向方面存在部分重叠，这可能暗示存在一种共同的靶向机制，因为MERS nsp1优先靶向核转录本。我们的相互作用组数据显示nsp1相互作用之间存在很大差异，这里测试的最小的nsp1即229E nsp1与最多数量的宿主蛋白相互作用。尽管nsp1是一种在不同冠状病毒中功能保守的相当保守的蛋白，但我们的数据表明其对宿主细胞的确切影响具有病毒特异性。
