Decoding Translation-Related Functional Sequences in 5ÚTRs Using Interpretable Deep Learning Models

Understanding how 5' untranslated regions (5ÚTRs) regulate mRNA translation is critical for controlling protein expression and designing effective therapeutic mRNAs. While recent deep learning models have shown promise in predicting translational efficiency from 5ÚTR sequences, most are constrained by fixed input lengths and limited interpretability. We introduce UTR-STCNet, a Transformer-based architecture for flexible and biologically grounded modeling of variable-length 5ÚTRs. UTR-STCNet integrates a Saliency-Aware Token Clustering (SATC) module that iteratively aggregates nucleotide tokens into multi-scale, semantically meaningful units based on saliency scores. A Saliency-Guided Transformer (SGT) block then captures both local and distal regulatory dependencies using a lightweight attention mechanism. This combined architecture achieves efficient and interpretable modeling without input truncation or increased computational cost. Evaluated across three benchmark datasets, UTR-STCNet consistently outperforms state-of-the-art baselines in predicting mean ribosome load (MRL), a key proxy for translational efficiency. Moreover, the model recovers known functional elements such as upstream AUGs and Kozak motifs, highlighting its potential for mechanistic insight into translation regulation.