Chen Yen-Lin, He Weiwei, Kirmizialtin Serdal, Pollack Lois
School of Applied and Engineering Physics, Cornell University, Ithaca, NY 14853, USA.
These authors contributed equally.
Cell Rep Phys Sci. 2022 Jul 20;3(7). doi: 10.1016/j.xcrp.2022.100971. Epub 2022 Jul 11.
RNA triple helices are commonly observed tertiary motifs that are associated with critical biological functions, including signal transduction. Because the recognition of their biological importance is relatively recent, their full range of structural properties has not yet been elucidated. The integration of solution wide-angle X-ray scattering (WAXS) with molecular dynamics (MD) simulations, described here, provides a new way to capture the structures of major-groove RNA triplexes that evade crystallographic characterization. This method yields excellent agreement between measured and computed WAXS profiles and allows for an atomically detailed visualization of these motifs. Using correlation maps, the relationship between well-defined features in the scattering profiles and real space characteristics of RNA molecules is defined, including the subtle conformational variations in the double-stranded RNA upon the incorporation of a third strand by base triples. This readily applicable approach has the potential to provide insight into interactions that stabilize RNA tertiary structure that enables function.
RNA三链螺旋是常见的三级结构基序，与包括信号转导在内的关键生物学功能相关。由于对其生物学重要性的认识相对较新，其完整的结构特性尚未阐明。本文所述的溶液广角X射线散射（WAXS）与分子动力学（MD）模拟相结合，提供了一种新方法来捕捉逃避晶体学表征的大沟RNA三链体结构。该方法在测量的和计算的WAXS图谱之间产生了极好的一致性，并允许对这些基序进行原子水平的详细可视化。使用相关图，定义了散射图谱中明确特征与RNA分子实空间特征之间的关系，包括双链RNA在通过碱基三联体掺入第三条链时的细微构象变化。这种易于应用的方法有可能深入了解稳定RNA三级结构从而实现功能的相互作用。
