RNADSN: Transfer-Learning 5-Methyluridine (m⁵U) Modification on mRNAs from Common Features of tRNA

One of the most abundant non-canonical bases widely occurring on various RNA molecules is 5-methyluridine (m5U). Recent studies have revealed its influences on the development of breast cancer, systemic lupus erythematosus, and the regulation of stress responses. The accurate identification of m⁵U sites is crucial for understanding their biological functions. We propose RNADSN, the first transfer learning deep neural network that learns common features between tRNA m⁵U and mRNA m⁵U to enhance the prediction of mRNA m⁵U. Without seeing the experimentally detected mRNA m⁵U sites, RNADSN has already outperformed the state-of-the-art method, m5UPred. Using mRNA m⁵U classification as an additional layer of supervision, our model achieved another distinct improvement and presented an average area under the receiver operating characteristic curve (AUC) of 0.9422 and an average precision (AP) of 0.7855. The robust performance of RNADSN was also verified by cross-technical and cross-cellular validation. The interpretation of RNADSN also revealed the sequence motif of common features. Therefore, RNADSN should be a useful tool for studying m⁵U modification.