Analysis of RNA translation with a deep learning architecture provides new insight into translation control.

Journal: Nucleic acids research
PMID:

Abstract

Accurate annotation of coding regions in RNAs is essential for understanding gene translation. We developed a deep neural network to directly predict and analyze translation initiation and termination sites from RNA sequences. Trained with human transcripts, our model learned hidden rules of translation control and achieved a near perfect prediction of canonical translation sites across entire human transcriptome. Surprisingly, this model revealed a new role of codon usage in regulating translation termination, which was experimentally validated. We also identified thousands of new open reading frames in mRNAs or lncRNAs, some of which were confirmed experimentally. The model trained with human mRNAs achieved high prediction accuracy of canonical translation sites in all eukaryotes and good prediction in polycistronic transcripts from prokaryotes or RNA viruses, suggesting a high degree of conservation in translation control. Collectively, we present TranslationAI (https://www.biosino.org/TranslationAI/), a general and efficient deep learning model for RNA translation that generates new insights into the complexity of translation regulation.

Authors

  • Xiaojuan Fan
    Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Tiangen Chang
    Laboratory of Cancer Data Science, National Cancer Institute, Bethesda, MD 20814, United States.
  • Chuyun Chen
    Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Markus Hafner
    RNA Molecular Biology Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Disease, Bethesda, MD 20814, United States.
  • Zefeng Wang
    CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: wangzefeng@picb.an.cn.