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Hepatitis Delta Virus histone mimicry drives the recruitment of chromatin remodelers for viral RNA replication.
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-21 , DOI: 10.1038/s41467-020-14299-9
Natali Abeywickrama-Samarakoon 1 , Jean-Claude Cortay 1 , Camille Sureau 2 , Susanne Müller 3 , Dulce Alfaiate 1, 4, 5 , Francesca Guerrieri 1, 6 , Apirat Chaikuad 3 , Martin Schröder 3 , Philippe Merle 1, 7 , Massimo Levrero 1, 6, 7 , Paul Dény 1, 8
Affiliation  

Hepatitis Delta virus (HDV) is a satellite of Hepatitis B virus with a single-stranded circular RNA genome. HDV RNA genome synthesis is carried out in infected cells by cellular RNA polymerases with the assistance of the small hepatitis delta antigen (S-HDAg). Here we show that S-HDAg binds the bromodomain (BRD) adjacent to zinc finger domain 2B (BAZ2B) protein, a regulatory subunit of BAZ2B-associated remodeling factor (BRF) ISWI chromatin remodeling complexes. shRNA-mediated silencing of BAZ2B or its inactivation with the BAZ2B BRD inhibitor GSK2801 impairs HDV replication in HDV-infected human hepatocytes. S-HDAg contains a short linear interacting motif (SLiM) KacXXR, similar to the one recognized by BAZ2B BRD in histone H3. We found that the integrity of the S-HDAg SLiM sequence is required for S-HDAg interaction with BAZ2B BRD and for HDV RNA replication. Our results suggest that S-HDAg uses a histone mimicry strategy to co-activate the RNA polymerase II-dependent synthesis of HDV RNA and sustain HDV replication.

中文翻译:

肝炎三角洲病毒组蛋白模拟驱动染色质重塑剂的募集以用于病毒RNA复制。

三角洲乙型肝炎病毒(HDV)是乙肝病毒的卫星,具有单链环状RNA基因组。HDV RNA基因组合成是在小肝炎三角洲抗原(S-HDAg)的帮助下,通过细胞RNA聚合酶在感染的细胞中进行的。在这里,我们显示S-HDAg结合与锌指结构域2B(BAZ2B)蛋白相邻的溴结构域(BRD),BAZ2B相关重塑因子(BRF)ISWI染色质重塑复合物的调节亚基。shRNA介导的BAZ2B沉默或被BAZ2B BRD抑制剂GSK2801灭活会损害HDV在感染HDV的人类肝细胞中的复制。S-HDAg包含一个短的线性相互作用基序(SLiM)KacXXR,类似于BAZ2B BRD在组蛋白H3中识别的一个。我们发现,S-HDAg与BAZ2B BRD相互作用以及HDV RNA复制需要S-HDAg SLiM序列的完整性。我们的结果表明,S-HDAg使用组蛋白模仿策略来共同激活HDV RNA的RNA聚合酶II依赖性合成并维持HDV复制。
更新日期:2020-01-22
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