Biology subjects

Benova, N.

Publications and source records attributed to Benova, N..

3 recordsLinked to original sources

bioRxiv2025

Prioritising Functional Noncoding Variants via eRNA Post-transcriptional Interaction Maps in Human Samples

Noncoding variants and mutations outnumber their coding counterparts but remain challenging to interpret functionally. We present TranCi, a method that prioritises human genetic variations by integrating enhancer RNA (eRNA) expression with eRNA-mRNA interactome maps. By linking variant-associated changes in eRNA to downstream gene regulation, TranCi captures functional effects missed by sequence-based or chromatin-centric approaches. In esophageal squamous cell cancer, TranCi identifies noncoding mutations with roles in disease initiation and progression. A personalised mode enables analysis at single-patient resolution, uncovering potential individual-specific regulatory variants. TranCi thus provides a mechanistic framework for interpreting noncoding variations and uniquely identifies their downstream targets, where standard methods often fall short. TranCi is available as a module within the eRNAkit R package (https://github.com/AneneLab/eRNAkit), leveraging its database of eRNA expression and interactions for functional variant interpretation.

genomics↗

bioRxiv2025

eRNAs Modulate mRNA Stability and Translation Efficiency to Bridge Transcriptional and Post-transcriptional Gene Regulation

Enhancer RNAs (eRNAs) are best known for their role in transcriptional regulation, where they facilitate enhancer-promoter communication and chromatin remodelling. Yet growing evidence suggests that their function may extend beyond the nucleus. Here, we systematically characterise the decay kinetics of eRNAs across human cell types using time-resolved transcriptomics and kinetic modelling. While most eRNAs undergo canonical exponential decay, a subset displays non-linear dynamics, suggesting context-dependent degradation mechanisms. Perturbation of core decay regulators, including components of the m6A and CCR4-NOT pathways, reveals that eRNA stability is modulated by a patchwork of pathways governing mRNA turnover. Integrating transcriptome-wide ribosome profiling, RNA-Seq, and half-life data, we identify eRNAs associated with changes in mRNA stability and translation efficiency of their target protein-coding transcripts. Functional validation of one such eRNA, en4528, shows it regulates CDKN2C mRNA independently of transcription and impacts cell migration. These findings redefine the regulatory scope of eRNAs, positioning them as active participants in post-transcriptional gene control and cellular behaviour. The resulting decay profiles and regulatory annotations have been incorporated into the eRNAkit database, available at https://github.com/AneneLab/eRNAkit, enhancing its capacity for integrative systems-level analysis of eRNA function.

molecular biology↗

bioRxiv2025

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

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.

molecular biology↗