Effects Of Non-synonymous Cassettes Alternative Splicing On Translation Regulation Of Its Products

Alternative splicing events are a basic and important regulatory mechanism in eukaryotes.Cassette alternative splicing events account for 35%of the total number of alternative splicing events,which is the most common type of splicing events.According to whether the number of bases in the alternative splicing region is a multiple of 3,cassette alternative splicing events can be divided into two categories:Synonymous cassette alternative splicing events and non-synonymous cassette alternative splicing events.Because non-synonymous cassette alternative splicing events will cause the code shift of gene coding frame,resulting in the destruction or modification of splicing product proteins and affecting biological physiological functions,the study of non-synonymous cassette alternative splicing events is of great significance.Taking the non-synonymous cassette alternative splicing events in miso database as the research object,this paper analyzes the impact of non-synonymous cassette alternative splicing events on the translation regulation of their products from the two levels of gene and protein,and constructs the product prediction model of non-synonymous cassette alternative splicing events to realize the structure prediction of the product protein of nonsynonymous cassette alternative splicing events.The specific work is as follows:(1)The effects of non-synonymous cassette alternative splicing events were analyzed at the gene and protein levels.Firstly,the non-synonymous cassette alternative splicing events were obtained from miso database,and the data set of non-synonymous cassette alternative splicing events was constructed.Then,the non-synonymous cassette alternative splicing events with product proteins before and after splicing were analyzed.Finally,the splicing preference of non-synonymous cassette alternative splicing events in 26 pathological tissues recorded in TCGA database was analyzed.The analysis results show that 57.9%of the cassette alternative splicing events in miso database are non-synonymous cassette alternative splicing events.2717 non-synonymous cassette alternative splicing events have proteins before and after splicing.Non-synonymous cassette alternative splicing events usually lead to the shortening of the product protein sequence,Splicing events in 26 diseased tissues recorded in TCGA database preferred that exons were spliced.(2)The prediction model of non-synonymous cassette alternative splicing event product was constructed to predict the structure of non-synonymous cassette alternative splicing event product protein.Three kinds of protein disorder structure prediction models of non-synonymous cassette alternative splicing products were constructed by LSTM:one is the protein structure prediction model of non-synonymous cassette alternative splicing products based on amino acid sequence information;The second is the protein structure prediction model of non-synonymous cassette alternative splicing products based on nucleic acid sequence information;The third is the protein structure prediction model of non-synonymous cassette alternative splicing products based on the information fusion of amino acid sequence and nucleic acid sequence.The prediction results show that the prediction accuracy of the model based on nucleic acid sequence information is slightly lower than that based on amino acid sequence information,and the prediction accuracy of the model based on fusion information is slightly higher than that based on nucleic acid sequence and amino acid sequence.This shows that nucleotides can not only encode the components of amino acid sequence,but also determine the folding structure of amino acid sequence.