Local changes in viral RNA sequence drive global changes in influenza nucleoprotein binding.
Local changes in viral RNA sequence drive global changes in influenza nucleoprotein binding.
复制标题
病毒RNA序列的局部变化驱动流感核蛋白结合的整体变化。
DOI：
10.1002/jmv.28896
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发表时间：
2023
影响因子：
12.7
通讯作者：
Lee,Nara
中科院分区：
文献类型：
--
作者：
LeSage,Valerie;Kanarek,JackP;Lakdawala,SeemaS;Lee,Nara
甲型流感病毒（IAV）的基因组由八个被病毒核蛋白（NP）包被的反义RNA片段组成。直到最近，人们还认为NP沿着整个片段均匀地结合病毒基因组RNA（vRNA）。然而，全基因组研究已经修改了原始模型，因为NP优先结合vRNA的某些区域，而其他区域则耗尽了NP结合。即使具有高序列相似性的菌株也表现出不同的NP结合谱。因此，仍然不知道如何建立NP对vRNA的结合特异性。在这里，我们引入核苷酸的变化vRNA检查是否一级序列可以影响NP结合。我们的研究结果表明，NP结合确实容易受到序列改变的影响，因为NP峰可能会丢失或在突变位点重新出现。出乎意料的是，核苷酸变化不仅影响突变位点的NP结合，而且影响未修饰的远端区域的NP结合。两者合计，我们的研究结果表明，NP结合不受一级序列单独，但由多个片段形成的网络管理NP的沉积vRNA。
The genome of influenza A viruses (IAV) consists of eight negative‐sense RNA segments that are coated by viral nucleoprotein (NP). Until recently, it was assumed that NP binds viral genomic RNA (vRNA) uniformly along the entire segment. However, genome‐wide studies have revised the original model in that NP instead binds preferentially to certain regions of vRNA, while others are depleted for NP binding. Even strains with high sequence similarity exhibit distinct NP‐binding profiles. Thus, it remains unknown how NP‐binding specificity to vRNA is established. Here we introduced nucleotide changes to vRNA to examine whether primary sequence can affect NP binding. Our findings demonstrate that NP binding is indeed susceptible to sequence alterations, as NP peaks can be lost or appear de novo at mutated sites. Unexpectedly, nucleotide changes not only affect NP binding locally at the site of mutation, but also impact NP binding at distal regions that have not been modified. Taken together, our results suggest that NP binding is not regulated by primary sequence alone, but that a network formed by multiple segments governs the deposition of NP on vRNA.