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研究揭示RNA结合蛋白亚型的不同功能
作者:小柯机器人 发布时间:2019/11/19 13:52:22

美国华盛顿大学Ram Savan和加州大学圣地亚哥分校Matthew D. Daugherty团队合作揭示了RNA结合蛋白亚型ZAP-S和ZAP-L具有独特的抗病毒和免疫分辨功能。该项研究成果2019年11月18日在线发表在《自然—免疫学》上。

研究人员发现,RNA结合蛋白ZAP的亚型既起直接的抗病毒限制因子的作用,又起干扰素分解因子的作用。ZAP的短亚型结合并介导了几种宿主干扰素信使RNA的降解,因此可作为干扰素应答的负反馈调节剂。相反,ZAP的长亚型具有抗病毒功能,并且不调节干扰素。这两种亚型包含相同的RNA靶向结构域,但它们在细胞内定位上的差异调节了宿主与病毒RNA的特异性,这导致了先天免疫反应期间对病毒复制的不同影响。

据了解,对病毒感染的最初应答是有预期的,宿主抗病毒限制因子和病原体传感器不断检查细胞,以通过干扰素的合成和下游活性迅速引发抗病毒反应。清除病原体后,宿主完成这种抗病毒应答并恢复稳态的能力至关重要。

附:英文原文

Title: RNA-binding protein isoforms ZAP-S and ZAP-L have distinct antiviral and immune resolution functions

Author: Johannes Schwerk, Frank W. Soveg, Andrew P. Ryan, Kerri R. Thomas, Lauren D. Hatfield, Snehal Ozarkar, Adriana Forero, Alison M. Kell, Justin A. Roby, Lomon So, Jennifer L. Hyde, Michael Gale, Matthew D. Daugherty, Ram Savan

Issue&Volume: 2019-11-18

Abstract: The initial response to viral infection is anticipatory, with host antiviral restriction factors and pathogen sensors constantly surveying the cell to rapidly mount an antiviral response through the synthesis and downstream activity of interferons. After pathogen clearance, the host’s ability to resolve this antiviral response and return to homeostasis is critical. Here, we found that isoforms of the RNA-binding protein ZAP functioned as both a direct antiviral restriction factor and an interferon-resolution factor. The short isoform of ZAP bound to and mediated the degradation of several host interferon messenger RNAs, and thus acted as a negative feedback regulator of the interferon response. In contrast, the long isoform of ZAP had antiviral functions and did not regulate interferon. The two isoforms contained identical RNA-targeting domains, but differences in their intracellular localization modulated specificity for host versus viral RNA, which resulted in disparate effects on viral replication during the innate immune response.

DOI: 10.1038/s41590-019-0527-6

Source: https://www.nature.com/articles/s41590-019-0527-6

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex