Advancing viral RNA structure prediction: measuring the thermodynamics of pyrimidine-rich internal loops
Advancing viral RNA structure prediction: measuring the thermodynamics of pyrimidine-rich internal loops
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DOI：
10.1261/rna.059865.116
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发表时间：
2017-05-01
期刊：
影响因子：
4.5
通讯作者：
Schroeder, Susan J.
中科院分区：
文献类型：
--
作者：
Phan, Andy;Mailey, Katherine;Schroeder, Susan J.
准确的热力学参数可改善 RNA 结构预测，从而加速对 RNA 功能的理解和 RNA 药物结合位点的识别。许多病毒 RNA 结构，例如内部核糖体进入位点，具有内部环和凸起，它们是潜在的药物靶位点。目前用于预测内部环的模型偏向于小的、对称的嘌呤环，因此很难预测病毒 RNA 中经常出现的、具有 >6 个核苷酸 (nt) 的不对称、富含嘧啶的环。本文介绍了 40 个嘧啶环的新热力学数据，其中许多可以形成 UU 或质子化 CC 碱基对。尿嘧啶和质子化胞嘧啶碱基对稳定不对称内部环。提出了准确的预测规则，解释了 RNA 不对称内环的所有热力学测量。提出了大于 6 nt 的环的新环起始项，其不遵循先前的假设，即增加不对称性会破坏环的稳定性。自 2004 年上次更新以来，已测量了 126 个不对称或尺寸大于 2 x 2 的新环。这些新测量极大地加深了 RNA 热力学数据库并使其多样化。这些结果将有助于更好地预测更大、富含嘧啶并发生在病毒结构（例如内部核糖体进入位点）内的内部环。
Accurate thermodynamic parameters improve RNA structure predictions and thus accelerate understanding of RNA function and the identification of RNA drug binding sites. Many viral RNA structures, such as internal ribosome entry sites, have internal loops and bulges that are potential drug target sites. Current models used to predict internal loops are biased toward small, symmetric purine loops, and thus poorly predict asymmetric, pyrimidine-rich loops with >6 nucleotides (nt) that occur frequently in viral RNA. This article presents new thermodynamic data for 40 pyrimidine loops, many of which can form UU or protonated CC base pairs. Uracil and protonated cytosine base pairs stabilize asymmetric internal loops. Accurate prediction rules are presented that account for all thermodynamic measurements of RNA asymmetric internal loops. New loop initiation terms for loops with >6 nt are presented that do not follow previous assumptions that increasing asymmetry destabilizes loops. Since the last 2004 update, 126 new loops with asymmetry or sizes greater than 2 x 2 have been measured. These new measurements significantly deepen and diversify the thermodynamic database for RNA. These results will help better predict internal loops that are larger, pyrimidine-rich, and occur within viral structures such as internal ribosome entry sites.