非编码RNA的二维化学作图
Two-dimensional chemical mapping for non-coding RNAs
摘要：
非编码RNA分子折叠成精确的碱基配对模式，在遗传调控和蛋白质合成中发挥关键作用。我们在这里表明，耦合系统诱变与高通量SHAPE化学作图，使准确的碱基对推理的结构域从核糖体RNA，核酶，核糖开关。对于挑战先前化学/计算方法的六RNA基准，这种突变和映射策略给出了与晶体学数据一致的二级结构（2%错误率），包括对双甘氨酸核糖开关的盲测。通过建模的部分有序的RNA状态，该方法使第一次测试的“域间螺旋交换”的假设配体结合协同甘氨酸核糖开关。最后，突变和地图数据报告的三级接触内的非编码RNA，再加上罗塞塔/FARFAR算法，这些数据给出核苷酸分辨率的三维模型（5.7 α螺旋RMSD）的腺嘌呤核糖开关。这些结果突出了一个二维的化学策略推断的二级和三级结构，非编码RNA的行为的承诺。
英文摘要：
Non-coding RNA molecules fold into precise base pairing patterns to carry out critical roles in genetic regulation and protein synthesis. We show here that coupling systematic mutagenesis with high-throughput SHAPE chemical mapping enables accurate base pair inference of domains from ribosomal RNA, ribozymes, and riboswitches. For a six-RNA benchmark that challenged prior chemical/computational methods, this mutate-and-map strategy gives secondary structures in agreement with crystallographic data (2 % error rates), including a blind test on a double-glycine riboswitch. Through modeling of partially ordered RNA states, the method enables the first test of an 'interdomain helix-swap' hypothesis for ligand-binding cooperativity in a glycine riboswitch. Finally, the mutate-and-map data report on tertiary contacts within non-coding RNAs; coupled with the Rosetta/FARFAR algorithm, these data give nucleotide-resolution three-dimensional models (5.7 Å helix RMSD) of an adenine riboswitch. These results highlight the promise of a two-dimensional chemical strategy for inferring the secondary and tertiary structures that underlie non-coding RNA behavior.
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