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Dynamic extended folding: modeling the RNA secondary structures during co-transcriptional folding. (English) Zbl 1403.92199

Summary: For RNA secondary structure prediction, it is an important issue that how to deal with co-transcriptional folding during the RNA synthesis in the cell. On one hand, co-transcriptional folding, leads to the correct final structure of the whole RNA molecule. On the other hand, it may form the recognition sites for the progress of the transcription. Considering the hurdles in the experimental determination of RNA folding structures, we proposed a so-called “dynamic extended folding simulation” approach. We used two human pre-mRNA samples, the first functional \(\alpha\)-gene \(HBZ\) and the fifth \(\beta\)-gene \(HBB\), to “display” the co-transcriptional folding images in detail. The modeling process starts from the prediction of a 30-nucleotide (nt) sequence, then in each update 30 nts was extended, say, 1–30, 1–60, 1–90, 1–120,…, 1–1651 nts (for \(HBB\), 1–1606 nts). We selected the RNAstructure program to predict the folding secondary structures of all the segments. We defined “hairpin” as the unit of the secondary structure and analyzed the states of such unit during the sequential dynamic extended folding processes. We found that some hairpins are “conserved”, i.e., after its appearance, it always is there in the followed foldings. Some hairpins present partially in the folding segments, and some hairpins appear for only once or twice. This phenomenon vividly depicts the generation and adjusting of the temporal structural units during the co-transcriptional folding process. It is these “hairpins” that support the thermodynamically stable structure at the end of the RNA synthesis. They may also play a role in RNA splicing process and even in the folding structure of the synthesized protein.

MSC:

92D20 Protein sequences, DNA sequences

Software:

Mfold
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References:

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