ZNF598 Plays Distinct Roles in Interferon-Stimulated Gene Expression and Poxvirus Protein Synthesis.
ZNF598 Plays Distinct Roles in Interferon-Stimulated Gene Expression and Poxvirus Protein Synthesis.
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DOI：
10.1016/j.celrep.2018.03.132
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发表时间：
2018-05-01
期刊：
影响因子：
8.8
通讯作者：
Walsh D
中科院分区：
文献类型：
--
作者：
DiGiuseppe S;Rollins MG;Bartom ET;Walsh D
核糖体亚基蛋白的翻译后修饰是调控基因表达的重要手段。近年来，泛素连接酶ZNF 598对小RPs RPS10和RPS20的泛素化调控被发现在核糖体质量控制（RQC）过程中对内部多聚腺苷酸化mRNA的核糖体传感和停滞中起作用。在这里，我们发现，ZNF 598和RPS 10负调控干扰素刺激基因（ISG）在原代细胞中的表达，消耗诱导ISG的表达和广泛的抗病毒状态。然而，缺乏干扰素应答的细胞系显示，ZNF 598 E3连接酶活性和RPS 20的泛素化，而不是RPS 10，是痘病毒复制和痘病毒蛋白合成所特异性需要的，痘病毒蛋白的编码mRNA含有不寻常的5′ poly（A）前导序列。我们的研究结果揭示了ZNF 598及其下游RPS靶点的不同功能，一个负调控ISG表达和一系列病毒的感染，而另一个正被痘病毒利用。除了在核糖体质量控制过程中抑制poly（A）通读外，DiGiuseppe等人还报道了ZNF 598和RPS 10负调节干扰素刺激的基因表达（ISG）。然而，在缺乏ISG反应的细胞系中，ZNF 598泛素连接酶活性和RPS 20泛素化是痘病毒特异性需要的，痘病毒产生具有5′ poly（A）前导序列的不寻常mRNA。
Post-translational modification of ribosomal subunit proteins (RPs) is emerging as an important means of regulating gene expression. Recently, regulatory ubiquitination of small RPs RPS10 and RPS20 by the ubiquitin ligase ZNF598 was found to function in ribosome sensing and stalling on internally polyadenylated mRNAs during ribosome quality control (RQC). Here, we reveal that ZNF598 and RPS10 negatively regulate interferon-stimulated gene (ISG) expression in primary cells, depletion of which induced ISG expression and a broad antiviral state. However, cell lines lacking interferon responses revealed that ZNF598 E3 ligase activity and ubiquitination of RPS20, but not RPS10, were specifically required for poxvirus replication and synthesis of poxvirus proteins whose encoding mRNAs contain unusual 5′ poly(A) leaders. Our findings reveal distinct functions for ZNF598 and its downstream RPS targets, one that negatively regulates ISG expression and infection by a range of viruses while the other is positively exploited by poxviruses. In addition to repressing poly(A) readthrough during ribosome quality control, DiGiuseppe et al. report that ZNF598 and RPS10 negatively regulate interferon-stimulated gene expression (ISG). However, in cell lines lacking ISG responses, ZNF598 ubiquitin ligase activity and RPS20 ubiquitination are specifically required by poxviruses, which produce unusual mRNAs with 5′ poly(A) leaders.
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DOI：
10.1261/rna.060897.117
发表时间：
2017-05
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Sitron CS;Park JH;Brandman O
通讯作者：
Brandman O
替代性裂解和聚腺苷酸化：长而短。
影响因子：
13.8
作者：
Tian, Bin;Manley, James L.
通讯作者：
Manley, James L.
影响因子：
16.6
作者：
Garzia, Aitor;Jafarnejad, Seyed Mehdi;Sonenberg, Nahum
通讯作者：
Sonenberg, Nahum
影响因子：
2.1
作者：
Matsuda, Ryo;Ikeuchi, Ken;Inada, Toshifumi
通讯作者：
Inada, Toshifumi
影响因子：
5.3
作者：
Gandin, Valentina;Gutierrez, Gustavo J.;Ronaic, Ze'ev A.
通讯作者：
Ronaic, Ze'ev A.