A G-quadruplex motif in an envelope gene promoter regulates transcription and virion secretion in HBV genotype B.
A G-quadruplex motif in an envelope gene promoter regulates transcription and virion secretion in HBV genotype B.
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DOI：
10.1093/nar/gkx823
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发表时间：
2017-11-02
影响因子：
14.9
通讯作者：
Vivekanandan P
中科院分区：
文献类型：
--
作者：
Biswas B;Kandpal M;Vivekanandan P
HBV基因型致病性不同。此外，HBV在转录和病毒复制调控方面存在基因型特异性差异，但其潜在机制尚不清楚。在这里，我们发现preS 2/S基因启动子中存在G-四链体基序;该G-四链体仅在HBV基因型B中高度保守，但在其他HBV基因型中则不然。我们证明，这个G-四链体基序形成一个混合的分子内G-四链体结构。有趣的是，破坏HBV基因型B中G-四链体的突变降低了preS 2/S启动子活性，导致B型肝炎表面抗原（HBsAg）水平降低。G-四链体配体稳定了基因型B中的G-四链体，并增强了preS 2/S启动子活性。此外，在全长HBV基因型B构建体中破坏G-四链体的突变与受损的病毒体分泌相关。与启动子内的典型G-四链体（其是转录的负调节因子）相反，HBV的preS 2/S启动子中的G-四链体代表非常规的正调节元件。我们的研究结果突出了（a）G-四链体介导的HBV转录和病毒体分泌的增强和（B）DNA二级结构在病毒基因组中复杂的基因型特异性调控机制中的未知作用。
HBV genotypes differ in pathogenicity. In addition, genotype-specific differences in the regulation of transcription and virus replication exist in HBV, but the underlying mechanisms are unknown. Here, we show the presence of a G-quadruplex motif in the promoter of the preS2/S gene; this G-quadruplex is highly conserved only in HBV genotype B but not in other HBV genotypes. We demonstrate that this G-quadruplex motif forms a hybrid intramolecular G-quadruplex structure. Interestingly, mutations disrupting the G-quadruplex in HBV genotype B reduced the preS2/S promoter activity, leading to reduced hepatitis B surface antigen (HBsAg) levels. G-quadruplex ligands stabilized the G-quadruplex in genotype B and enhanced the preS2/S promoter activity. Furthermore, mutations disrupting the G-quadruplex in the full-length HBV genotype B constructs were associated with impaired virion secretion. In contrast to typical G-quadruplexes within promoters which are negative regulators of transcription the G-quadruplex in the preS2/S promoter of HBV represents an unconventional positive regulatory element. Our findings highlight (a) G-quadruplex mediated enhancement of transcription and virion secretion in HBV and (b) a yet unknown role for DNA secondary structures in complex genotype-specific regulatory mechanisms in virus genomes.
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影响因子：
14.9
作者：
Babinský M;Fiala R;Kejnovská I;Bednářová K;Marek R;Sagi J;Sklenář V;Vorlíčková M
通讯作者：
Vorlíčková M
DOI：
10.1038/nrg3296
发表时间：
2012-11
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
Paramasivan, Sattanathan;Rujan, Iulian;Bolton, Philip H.
通讯作者：
Bolton, Philip H.
影响因子：
4.4
作者：
Biswas B;Kandpal M;Jauhari UK;Vivekanandan P
通讯作者：
Vivekanandan P
影响因子：
14.9
作者：
Madireddy A;Purushothaman P;Loosbroock CP;Robertson ES;Schildkraut CL;Verma SC
通讯作者：
Verma SC