A Folding "Framework Structure" Of Tetrahymena Group Ⅰ Intron

We have published the dynamic extended folding (DEF) method, which is a RNA secondary structure prediction approach—to simulate the RNA co-transcriptional folding process in vivo. The 26S pre-ribosomal RNA intron of Tetrahymena thermophilia is a groupⅠintron ribozyme.The self-splicing reaction of Tetrahymena groupⅠintron depends on its secondary structure, which is highly conserved, and only correct structure like the natural state could have the activity. Since the particular function of the groupⅠintron of Tetrahymena was revealed, several algorithms and experimental methods have been used to analyze its secondary structure. As early as 1983, the free energy minimization and phylogenetics were applied to predict and publish the possible secondary structure of Tetrahymena groupⅠintron. With the progress of the technology, the determination of the structure becomes more and more sophisticated. Therefore, in the past decade, several articles on structure of group I intron had been published, and the latest X-ray crystallography structure (determined in 2008) reached the resolution of 1.95 .It is well-known that the natural protein structures are framed. We treated Tetrahymena groupⅠintron and the 335 human pre-mRNAs as well as their spliced mature mRNAs by using the described method and process with the physics concept of coarse-grained strategy. The large-sample comparison and analysis showed that the DEF approach can efficiently simulate the RNA folding process in cell and construct a simple and general framework structure.Our results show that the DEF framework structure of Tetrahymena group I intron reflects its function sites in a concise and straightforward manner, and the scope of the simulation was expanded. The high matched value of the crystal structure and the framework can not only reflect the advantages of this method, but also can provide a theoretical basis for the actual operation. The m/n values of our framework structure can prove the conservation of the hairpins, which explain why some hairpins can be measured easily. The hairpins with high m/n values have high stability, which could be measured easily; however, the structure with low m/n value is not measured. The m/n values can guide the experimenters to select the conservative structure to measure, which can save a lot of time, manpower and material resources.It is a great challenge to study structures and functions on RNA. It could cost a lot of time, manpower and material resources in experiment. It is difficult to get a crystal of RNA, especially full mRNA through the current experimental technique, then, developing theoretical simulation of RNA secondary structure is essential. The dynamic extended folding simulation method not only can provide a theoretical foundation for the experiments, but also can simulate the folding process of RNA in eukaryotic cells and finally obtain the simple, intuitive and vivid high-confidence framework.