Ule Lab
Welcome to the RNA networks lab
RNA is a multitalented molecule: it can store genetic information as well as catalyse chemical reactions. According to the RNA world hypothesis, these talents stem from the central role of RNA at the origin of life. In ‘modern’ cells, RNA molecules carry genetic information from DNA to proteins, and in addition they form wonderfully intricate networks of interactions with proteins and other molecules.
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We study how RNA networks direct the workings of a cell by regulating gene expression and protein homeostasis. RNAs are coated by proteins to form ribonucleoprotein complexes (RNPs). These proteins guide the RNA on its journey through the cell to regulate gene expression, while the RNAs also regulate the functions of bound proteins and thereby affect their homeostasis. To understand these RNA networks, we develop new techniques that reveal protein-RNA and RNA-RNA interactions within cells and interrogate their functions.
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In particular, we investigate how RNPs contribute to the functions of nerve cells in development, how they help us understand brain evolution, and how faulty RNPs lead to conditions affecting the nervous system, particularly neurodegenerative diseases such as amyotrophic lateral sclerosis. We hope our discoveries will open opportunities for new therapies for these diseases.
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Most team members are based at the UK Dementia Research Institute at King's College London, with additional members located in satellite teams at Francis Crick Institute in London and the Institute of Chemistry in Ljubljana, Slovenia:
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Dementia Research Institute centre at King's
In April 2022, we joined the Dementia Research Institute centre at King's College London, where most team members are based now. The centre is part of the Department of Basic and Clinical Neuroscience.
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Institute of Chemistry, Ljubljana, Slovenia
An RNA accelerator team at the institute of Chemisty in Ljubljana.
Recent publication highlight
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Faraway et al. (2025) Collective homeostasis of condensation-prone proteins via their mRNAs, Nature, Sept 24
Proteins that have similar disordered regions tend to condense together, so their equilibrium is a collective problem for the cell. How do the cells solve this? We reported the discovery of a mechanism that we’ve called ‘interstasis’, which promotes the equilibrium of co-condensing proteins. Focusing on a condensate called ‘nuclear speckles’, we found that increased concentration of mix-charged proteins within speckles induces the sequestration of the mRNAs that encode the same proteins. The condensation properties of nuclear speckles thus act as a sensor for interstasis, a collective feedback loop that co-regulates condensation-prone proteins. We showed that this mechanism relies on codon bias that promote repetitive signatures within coding sequences for condensation-prone proteins, so that specific RNA-binding proteins can recognise these signatures and capture the mRNAs when needed. Please take a look the paper and its summary.
A free Nextflow analysis web platform and database​
We're collaborating with the London startup Goodwright, who developed the web server flow.bio an end-to-end web platform for biology that allows scientists to run Nextflow omics pre-processing pipelines via a front-end web interface, including our CLIP-seq pipeline. Read more about it here.
Flow lets users share raw data, analyses, and finished results either as part of the public database, or with specified groups of researchers in one click. As it becomes populated with increasing amounts of public data, it will increasingly serve as a database of well-curated raw and processed data. Read more about its manuscript and documentation.
Recently published methods
iiCLIP: An improved iCLIP protocol that is technically convenient and efficient, enables quality control via non-radioactive analysis of protein-RNA complexes, and produces data of high specificity.
CLIP data analysis pipeline: nf-core/clipseq - a robust Nextflow pipeline for quality control and analysis of CLIP sequencing data.
Ultraplex: Software for user friendly, streamlined and robust demultiplexing of complex sequencing libraries, such as those produced by various CLIP and ribosome profiling protocols.
clipplotr: A command-line tool for visual comparative and integrative analyses with normalisation and smoothing options for data to be shown alongside reference annotation tracks and functional genomic data.
PEKA: Positionally-enriched k-mer analysis, a computational tool for analysis of enriched motifs from CLIP datasets, which minimises the impact of technical and regional genomic biases by internal data normalisation.
Ribocutter: A streamlined Cas9-based protocol for removing abundant rRNA/ncRNA contaminants from Ribo-seq, CLIP or other RNA-seq libraries and a software tool for designing ready-to-order sgRNA templates.
Riboseq-flow: A streamlined, reliable pipeline for ribosome profiling data analysis and quality control.
Tosca: a Nextflow computational pipeline for the processing, analysis and visualisation of proximity ligation sequencing data.
13C-dynamods: A 13C labeling approach to quantify the turnover of base modifications in newly transcribed RNA, which enables studies of the origin of modified RNAs and its dynamics under nonstationary conditions.
SPACE: Silica Particle Assisted Chromatin Enrichment to isolate global and regional chromatin components with high specificity and sensitivity, and SPACEmap to identify the chromatin-contact regions in proteins.
We moved south of the River Thames
On 1/4/22, the team moved from the Crick institute to KCL, where Jernej took the position of UK DRI Centre Director at King's. The primary London lab is now based at the King's Denmark Hill campus (within the Maurice Wohl institute), while a satellite lab of 3 people remains at the Francis Crick institute till end of 2027 to work on the Wellcome Trust project.