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bioRxiv · 10.1101/2025.04.25.650683

eRNAkit: Expanding the Functional Atlas of human Enhancer RNAs Beyond the Nucleus

Benova, N.·Kuklinkova, R.·Eldahshoury, M. K.·Anene, C. A.
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Abstract

Enhancer RNAs (eRNAs) are a class of non-coding RNAs transcribed from active enhancers that regulate various aspects of transcription. Although traditionally viewed as nuclear-localised and unstable transcripts, large transcriptomic studies reveal they vary widely in localisation and biochemical properties, including detectable accumulation in cytoplasmic compartments. These observations suggest potential non-nuclear functions for eRNAs, yet existing databases remain focused on nuclear, cis-regulatory roles, limiting systematic exploration of their broader regulatory repertoire. Here we present eRNAkit, a comprehensive and accessible resource designed to address this gap by integrating subcellular localisation, RNA-RNA interaction and expression data for annotated eRNAs. Leveraging fractionation-based RNA-Seq datasets, eRNAkit profiles eRNA distribution across nuclear and cytoplasmic compartments. It incorporates gene expression data spanning major human organs and primary cell types, enabling tissue-specific analysis of eRNA function. Crucially, eRNAkit includes experimentally derived RNA-RNA interaction data from RIC-Seq, PARIS, and KARR-Seq, supporting exploration of trans-acting and cytoplasmic roles for eRNAs grounded in physical interaction evidence. eRNAkit expands current eRNA resources beyond the enhancer-promoter paradigm, offering a robust platform for dissecting non-canonical functions of eRNAs and advancing our understanding of their full regulatory potential in human biology. The eRNAkit resource is available to download at https://github.com/AneneLab/eRNAkit.

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Benova, N., Kuklinkova, R., Eldahshoury, M. K., Anene, C. A.. 2025-04-25. eRNAkit: Expanding the Functional Atlas of human Enhancer RNAs Beyond the Nucleus. https://doi.org/10.1101/2025.04.25.650683

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