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.
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...
A. Kulikov, E. A. Sivoplyas, Oleg E. Lazebny· Genes· 0 citations
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...
Ya-Ning Li, Fang Ge, Lei Pan et al.· Journal of Chemical Informat...· 0 citations
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...
Shi-Yuan Chen, Neil R. Fernandes, Wei Vivian Li et al.· bioRxiv· 0 citations
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.
Ilya E. Vorontsov, N. Gryzunov, Bayley R. McDonald et al.· bioRxiv· 0 citations
The Vertebrate Regulatory MOdule Detector (VRMOD) provides a universal coordinate reference system for regulatory sequences across 309 vertebrate genomes and enables genome-wide annotation of non-coding regulatory elements in any vertebrate species using genomic sequence alone.
Tássia Mangetti Gonçalves, Casey L. Stewart, Samantha D. Baxley et al.· NAR Genomics and Bioinformat...· 0 citations
This Mini Review summarizes seq2func modelling in plant regulatory genomics, discusses plant-specific challenges and the complementary value of observational and perturbation assays, and proposes evaluation frameworks based on biologically meaningful distribution shifts.
Ming-Fang Zhan, Rui-Gang Wu· Frontiers in Plant Science· 0 citations
