Nucleic Acid Center, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, 5230 Odense M, Denmark.
RNA. 2012 May;18(5):992-1000. doi: 10.1261/rna.029918.111. Epub 2012 Mar 5.
In brome mosaic virus, both the replication of the genomic (+)-RNA strands and the transcription of the subgenomic RNA are carried out by the viral replicase. The production of (-)-RNA strands is dependent on the formation of an AUA triloop in the stem-loop C (SLC) hairpin in the 3'-untranslated region of the (+)-RNA strands. Two alternate hypotheses have been put forward for the mechanism of subgenomic RNA transcription. One posits that transcription commences by recognition of at least four key nucleotides in the subgenomic promoter by the replicase. The other posits that subgenomic transcription starts by binding of the replicase to a hairpin formed by the subgenomic promoter that resembles the minus strand promoter hairpin SLC. In this study, we have determined the three-dimensional structure of the subgenomic promoter hairpin using NMR spectroscopy. The data show that the hairpin is stable at 30°C and that it forms a pseudo-triloop structure with a transloop base pair and a nucleotide completely excluded from the helix. The transloop base pair is capped by an AUA triloop that possesses an extremely well packed structure very similar to that of the AUA triloop of SLC, including the formation of a so-called clamped-adenine motif. The similarities of the NMR structures of the hairpins required for genomic RNA and subgenomic RNA synthesis show that the replicase recognizes structure rather than sequence-specific motifs in both promoters.
在雀麦花叶病毒中,基因组 (+)RNA 链的复制和亚基因组 RNA 的转录都是由病毒复制酶进行的。(-)RNA 链的产生依赖于(+)RNA 链 3'非翻译区茎环 C(SLC)发夹中 AUA 三核苷酸环的形成。对于亚基因组 RNA 转录的机制,已经提出了两种替代假说。一种假设是,转录起始于复制酶识别亚基因组启动子中至少四个关键核苷酸。另一种假设是,亚基因组转录起始于复制酶与亚基因组启动子形成的发夹结合,该发夹类似于负链启动子发夹 SLC。在这项研究中,我们使用 NMR 光谱法确定了亚基因组启动子发夹的三维结构。数据表明,发夹在 30°C 下稳定,并且它形成具有反环碱基对和完全排除在螺旋之外的核苷酸的假三核苷酸环结构。反环碱基对由 AUA 三核苷酸环封闭,该三核苷酸环具有极其紧密堆积的结构,与 SLC 的 AUA 三核苷酸环非常相似,包括形成所谓的夹式腺嘌呤基序。基因组 RNA 和亚基因组 RNA 合成所需的发夹的 NMR 结构的相似性表明,复制酶在两个启动子中识别结构而不是序列特异性基序。