Tomaszewska Maria, Szabat Marta, Zielińska Karolina, Kierzek Ryszard
Department of Structural Chemistry and Biology of Nucleic Acids, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.
Department of Biomolecular NMR, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.
Int J Mol Sci. 2021 Jun 2;22(11):6031. doi: 10.3390/ijms22116031.
Influenza A virus (IAV) causes seasonal epidemics and sporadic pandemics, therefore is an important research subject for scientists around the world. Despite the high variability of its genome, the structure of viral RNA (vRNA) possesses features that remain constant between strains and are biologically important for virus replication. Therefore, conserved structural motifs of vRNA can represent a novel therapeutic target. Here, we focused on the presence of G-rich sequences within the influenza A/California/07/2009(H1N1) genome and their ability to form RNA G-quadruplex structures (G4s). We identified 12 potential quadruplex-forming sequences (PQS) and determined their conservation among the IAV strains using bioinformatics tools. Then we examined the propensity of PQS to fold into G4s by various biophysical methods. Our results revealed that six PQS oligomers could form RNA G-quadruplexes. However, three of them were confirmed to adopt G4 structures by all utilized methods. Moreover, we showed that these PQS motifs are present within segments encoding polymerase complex proteins indicating their possible role in the virus biology.
甲型流感病毒(IAV)引发季节性流行和散发性大流行,因此是全球科学家的重要研究对象。尽管其基因组具有高度变异性,但其病毒RNA(vRNA)的结构具有在不同毒株间保持不变且对病毒复制具有生物学重要性的特征。因此,vRNA的保守结构基序可代表一种新的治疗靶点。在此,我们聚焦于甲型流感病毒/加利福尼亚/07/2009(H1N1)基因组中富含G的序列的存在及其形成RNA G-四链体结构(G4s)的能力。我们鉴定出12个潜在的四链体形成序列(PQS),并使用生物信息学工具确定了它们在IAV毒株中的保守性。然后我们通过各种生物物理方法研究了PQS折叠成G4s的倾向。我们的结果表明,6个PQS寡聚体能形成RNA G-四链体。然而,其中3个通过所有使用的方法均被证实采用了G4结构。此外,我们表明这些PQS基序存在于编码聚合酶复合蛋白的片段中,表明它们在病毒生物学中可能发挥的作用。