Gultyaev Alexander P, Tsyganov-Bodounov Anton, Spronken Monique I J, van der Kooij Sander, Fouchier Ron A M, Olsthoorn René C L
Department of Viroscience, Erasmus Medical Center, The Netherlands; Leiden Institute of Advanced Computer Science (LIACS), Leiden University, Niels Bohrweg 1, The Netherlands;
Leiden Institute of Chemistry, Leiden University, P.O.Box 9502, 2300 RA Leiden, The Netherlands;; Current address: Illumina UK Ltd., Chesterford Research Park, Little Chesterford, Essex, UK;
RNA Biol. 2014;11(7):942-52. doi: 10.4161/rna.29730. Epub 2014 Jul 23.
Conserved RNA secondary structures were predicted in the nucleoprotein (NP) segment of the influenza A virus genome using comparative sequence and structure analysis. A number of structural elements exhibiting nucleotide covariations were identified over the whole segment length, including protein-coding regions. Calculations of mutual information values at the paired nucleotide positions demonstrate that these structures impose considerable constraints on the virus genome evolution. Functional importance of a pseudoknot structure, predicted in the NP packaging signal region, was confirmed by plaque assays of the mutant viruses with disrupted structure and those with restored folding using compensatory substitutions. Possible functions of the conserved RNA folding patterns in the influenza A virus genome are discussed.
利用比较序列和结构分析方法，对甲型流感病毒基因组的核蛋白（NP）片段中的保守RNA二级结构进行了预测。在整个片段长度上，包括蛋白质编码区，鉴定出了许多表现出核苷酸共变的结构元件。对配对核苷酸位置的互信息值计算表明，这些结构对病毒基因组进化施加了相当大的限制。通过对结构破坏的突变病毒和使用补偿性替换恢复折叠的病毒进行蚀斑试验，证实了在NP包装信号区域预测的假结结构的功能重要性。讨论了甲型流感病毒基因组中保守RNA折叠模式的可能功能。
