Department of Theoretical Chemistry, University of Vienna, Vienna, Austria.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Bioinformatics. 2023 Jan 1;39(1). doi: 10.1093/bioinformatics/btad034.
Folding during transcription can have an important influence on the structure and function of RNA molecules, as regions closer to the 5' end can fold into metastable structures before potentially stronger interactions with the 3' end become available. Thermodynamic RNA folding models are not suitable to predict structures that result from cotranscriptional folding, as they can only calculate properties of the equilibrium distribution. Other software packages that simulate the kinetic process of RNA folding during transcription exist, but they are mostly applicable for short sequences.
We present a new algorithm that tracks changes to the RNA secondary structure ensemble during transcription. At every transcription step, new representative local minima are identified, a neighborhood relation is defined and transition rates are estimated for kinetic simulations. After every simulation, a part of the ensemble is removed and the remainder is used to search for new representative structures. The presented algorithm is deterministic (up to numeric instabilities of simulations), fast (in comparison with existing methods), and it is capable of folding RNAs much longer than 200 nucleotides.
This software is open-source and available at https://github.com/ViennaRNA/drtransformer.
Supplementary data are available at Bioinformatics online.
在转录过程中，折叠可以对 RNA 分子的结构和功能产生重要影响，因为靠近 5' 端的区域可以在与 3' 端可能更强的相互作用变得可用之前折叠成亚稳态结构。热力学 RNA 折叠模型不适合预测由共转录折叠产生的结构，因为它们只能计算平衡分布的性质。其他模拟转录过程中 RNA 折叠动力学过程的软件包存在，但它们主要适用于短序列。
我们提出了一种新的算法，用于跟踪转录过程中 RNA 二级结构整体的变化。在每个转录步骤中，都会识别出新的代表性局部最小值，定义邻域关系，并估计动力学模拟的跃迁速率。在每次模拟之后，都会移除部分集合，并使用剩余部分搜索新的代表性结构。所提出的算法是确定性的（在模拟的数值不稳定性范围内），速度快（与现有方法相比），并且能够折叠比 200 个核苷酸长的 RNA。
该软件是开源的，可在 https://github.com/ViennaRNA/drtransformer 上获得。
补充数据可在生物信息学在线获得。
