CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
BMC Bioinformatics. 2020 Oct 24;21(1):478. doi: 10.1186/s12859-020-03818-6.
Introns have been shown to be spliced in a defined order, and this order influences both alternative splicing regulation and splicing fidelity, but previous studies have only considered neighbouring introns. The detailed intron splicing order remains unknown.
In this work, a method was developed that can calculate the intron splicing orders of all introns in each transcript. A simulation study showed that this method can accurately calculate intron splicing orders. I further applied this method to real S. pombe, fruit fly, Arabidopsis thaliana, and human sequencing datasets and found that intron splicing orders change from gene to gene and that humans contain more not in-order spliced transcripts than S. pombe, fruit fly and Arabidopsis thaliana. In addition, I reconfirmed that the first introns in humans are spliced slower than those in S. pombe, fruit fly, and Arabidopsis thaliana genome-widely. Both the calculated most likely orders and the method developed here are available on the web.
A novel computational method was developed to calculate the intron splicing orders and applied the method to real sequencing datasets. I obtained intron splicing orders for hundreds or thousands of genes in four organisms. I found humans contain more number of not in-order spliced transcripts.
已经证实内含子按照特定的顺序被剪接,并且这种顺序会影响可变剪接调控和剪接保真度,但之前的研究仅考虑了相邻的内含子。详细的内含子剪接顺序仍然未知。
在这项工作中,开发了一种可以计算每个转录本中所有内含子剪接顺序的方法。模拟研究表明,该方法可以准确地计算内含子剪接顺序。我进一步将该方法应用于真实的酿酒酵母、果蝇、拟南芥和人类测序数据集,发现内含子剪接顺序因基因而异,并且人类中包含的未按顺序剪接的转录本比酿酒酵母、果蝇和拟南芥多。此外,我重新证实了人类的第一个内含子在基因组范围内比酿酒酵母、果蝇和拟南芥剪接得更慢。计算出的最可能的顺序和这里开发的方法都可以在网上获得。
开发了一种新的计算方法来计算内含子剪接顺序,并将该方法应用于真实的测序数据集。我获得了四个生物体中数百个或数千个基因的内含子剪接顺序。我发现人类中包含更多数量的未按顺序剪接的转录本。