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EukaUTR: a foundation model for functional modelling and design of eukaryotic 3′ UTRs

Sep 2026 · bioRxiv · 0 citations · 43 references
Biology

Abstract

Eukaryotic mRNA 3′ UTRs encode regulatory signals that shape post-transcriptional regulation, RNA fate and gene expression. However, a foundation model that spans broad eukaryotic 3′ UTR sequence space while unifying prediction, interpretation and design within a single framework is still lacking. Here we present EukaUTR, a 3′ UTR-specific foundation model trained on a large-scale eukaryotic 3′ UTR sequence corpus spanning diverse evolutionary lineages. Across 13 prediction tasks of post-transcriptional regulation, RNA fate and expression output, EukaUTR showed strong transferability, achieving relative improvements of up to 27.45% over the strongest baselines. Extending these capabilities to sequence design, EukaUTR generated novel 3′ UTRs that captured natural sequence patterns and regulatory features and EukaUTR-Guide extracted stability signals from small sets of 3′ UTRs to guide editing toward enhanced predicted stability. Together, EukaUTR establishes a sequence-to-function-to-design framework that connects broad eukaryotic representation learning with transferable functional prediction and mRNA design.

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