Genomics of Long noncoding RNA and Disease
We develop (non-coding) RNA therapeutics for incurable diseases using genomics and bioinformatics.
PI: Rory Johnson
Our mission is to develop better therapies for common diseases through understanding the original molecule of Life: RNA.
We develop tools based on CRISPR-Cas genome-editing and bioinformatics to discover and drug disease-causing RNAs.
We focus on the important yet mysterious class of long noncoding RNAs (lncRNAs).
We are an interdisciplinary, international research group based at University College Dublin.
Pan-cancer discovery of driver mutations in long noncoding RNAs reveals widespread functional rewiring of RNA regulatory elements
June 2026
Sunandini Ramnarayanan · Roofiya Koya · et al. · Rory Johnson*
We analyse 12,631 cancer genomes from the 100,000 Genomes Project to identify 121 lncRNAs under positive selection across 19 cancer types. Approximately two-thirds of tumours harbour at least one lncRNA driver mutation. Somatic mutations preferentially remodel RNA-binding protein interaction sites, liberating oncogenic lncRNAs including MALAT1, SNHG14 and NEAT1 — uncovering a new class of cancer drivers and targets for RNA-directed therapies.
Fig. a Study design and proposed mechanism linking lncRNA somatic mutations to tumour formation.
Fig. b Model: somatic mutations disrupt repressive RNA:protein interactions to stabilise oncogenic lncRNAs in tumour cells.
Organisational principles of long non-coding RNAs revealed by exon deletion
Sarang S Bhutada · Hugo A Guillen-Ramirez · Tina Uroda · et al. · Rory Johnson*
We establish a high-throughput CRISPR-Cas9 strategy to dissect lncRNA functional architecture at exon resolution, screening 358 exons from 107 lncRNAs across four human cell lines. We find that only a minority of exons are functional in any given cell line, with functionality enriched towards the transcript start. Through statistical and experimental analyses, lncRNA function is shown to depend on transposable elements, microRNA response elements and RNA-binding protein sites — broadly supporting a modular organisation for lncRNAs and expanding the catalogue of experimentally defined functional elements by an order of magnitude.
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Model of lncRNA functional organisation. lncRNA genes harbour discrete functional elements within a minority of exons. These elements mediate cell-type-specific interactions with distinct proteins, while the majority of exons remain non-functional.
