Deciphering the comprehensive relationship between 5′ UTR and 3′ UTR sequences with deep learning

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ID: 326483
2026
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Abstract
MOTIVATION: Recent advances in mRNA therapeutics have driven further research on the untranslated regions (UTRs) of mRNA. However, prior studies have mainly focused on either the 5' or 3' UTR individually. Increasing evidence suggests potential cooperative effects between these two regions, which remain largely unexplored in computational studies. RESULTS: We present a deep learning-based approach to predicting relationships between 5' and 3' UTRs by leveraging latent representations from a pre-trained RNA language model and contrastive learning. Our method effectively identifies highly related UTRs, uncovering sequence and expression characteristics that suggest functional interplay. Our analysis revealed that Highly Related UTRs (HRUs) are significantly enriched in genes associated with neural development, exhibit distinctive UTR length and secondary structure characteristics, and are involved in cell type-specific regulation of translation efficiency. These findings provide new insights into UTR co-optimization for mRNA therapeutics. AVAILABILITY: The source code is available for free at https://github.com/hmdlab/utr\_pairpred.git. The data and intermediate files used in our analysis are available at https://waseda.box.com/v/utr-pairpred-data.
Reference Key
openalex_W4410598898 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Kanta Suga, Keisuke Yamada, Michiaki Hamada
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Journal BMC Bioinformatics
Year 2026
DOI
10.1093/bioinformatics/btag634
URL
https://doi.org/10.1093/bioinformatics/btag634
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