Across 13 prediction tasks spanning post-transcriptional regulation, RNA fate and expression output, EukaUTR models matched or exceeded the strongest external baselines on nearly all tasks, with relative improvements of up to 27.45%.
Abstract
Eukaryotic mRNA 3′ UTRs encode regulatory information that shapes post-transcriptional control, RNA fate and gene expression. However, a 3′ UTR-specific foundation model that spans broad eukaryotic sequence diversity while supporting both functional prediction and sequence design is 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 spanning post-transcriptional regulation, RNA fate and expression output, EukaUTR models matched or exceeded the strongest external baselines on nearly all tasks, with relative improvements of up to 27.45%. EukaUTR also generated de novo 3′ UTRs with natural-like sequence and regulatory properties. EukaUTR-Guide further derived stability-associated signals from small sequence sets to guide editing towards enhanced predicted stability. Together, EukaUTR provides a sequence-to-function-to-design framework for transferable 3′ UTR modelling and design.
Background/Objectives: The 3′ untranslated region (3′ UTR) integrates cleavage and polyadenylation signals, microRNA targets, RNA-binding-protein sites, and RNA secondary structure, but the organizational levels that remain conserved during long-term sequence evolution are poorly understood. Methods: We analyzed the ra...
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Genetic variants in untranslated regions (UTRs) can alter post-transcriptional regulation, yet functional interpretation remains difficult because regulatory mechanisms differ between 5′UTR and 3′UTR contexts and are not fully captured by generic noncoding-variant scores. We developed UTR-FNex, an interpretable machi...
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RNA plays central roles in regulating information flow and provides a versatile substrate for engineering biological functions. While large language models (LLMs) have transformed natural language processing and protein design, a general framework connecting RNA foundation models to functional sequence design remains l...
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EPIC, the Eukaryotic Promoter and transcription Initiation prediction Challenge, relies on understudied animals spanning three phyla: octopus, oyster, milkweed bug, Indian meal moth, and shark and is open to everyone.
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