System Biological Study On MRNA M~6A Sites Prediction And Function Identification

N~6-Methyladenosine(m~6A)is the most prevalent and abundant modification in mRNA that has been linked to many key biological processes.High-throughput experiments like MeRIP-seq and mi-CLIP have generated m~6A peaks and sites across the transcriptome,but the transcriptome-wide m~6A profiles are only mapped in a limited number of species and tissues.To get more potential accurate m~6A sites,in silico prediction of m~6A sites is a good solution.On the other hand,researchers found that m~6A plays important roles in the mRNA metabolism including alternative splicing,transport,translation and mRNA decay.As reported,m~6A functions in circadian rhythm maintenance and cell cycle regulation,as well as in cell differentiation and reprogramming.Due to the effect of m~6A on mRNA metabolism,abnormal m~6A level may contribute to the development of many diseases including cancer.In this work,we conducted in silico predition of m~6A site based on Support Vector Machine.We analysed the m~6A peaks or sites produced by high-throughput methods,extracted multiple features including the sequence around the sites,the local secondary structure and the relative position of the site in mRNA.Using these features,we trained SVM models to predict m~6A sites of mRNA.So far,we have built the prediction models of Arabidopsis thaliana and mammals,which achieved good performance.Friendly websites for m~6A prediction and query were constructed,named AthMethPre for A.thaliana and RNAMethPre for mammals.Since the function of m~6A in cancer is still not well revealed,we firstly analysed the potential regulatory role of m~6A in cancer.Making use of the transcriptome-wide m~6A profiles and the cancer somatic mutations identified by the Whole Exome Sequencing,we identified a list of potential mutated m~6A sites in UTR region or as synonymous in cancer.The mutation of m~6A sites may inhibit the methylation of the mRNA at the specific sites,thus affecting the function of the genes.Functional analysis of the genes barbored m~6A sites revealed that many of them are associated with cancer,indicating that m~6A may play important roles in cancer.The pionner work provides solid foundations for the further research about the function of m~6A mutations in cancer.