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.
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.
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.
Institute of Chemistry, Ljubljana, Slovenia
An ERC grant, co-hosted at the Ljubljana Chemistry Institute, funds a satellite team at the institute until 2025.
Recent publication highlight
Modic et al. (2024) Poised PABP-RNA hubs implement signal-dependent mRNA decay in development, Nature Str Mol Biol, Jul 25
How can cellular signalling quickly change the set of expressed genes (transcriptome) to drive fast biological changes? We used deep learning and a range of systems-biology techniques to discover dynamic RNA binding patterns, or ‘mRNA hubs’, at the ends of mRNAs that control a developmental cell fate transition. These mRNA hubs undergo major changes in ribonucleoprotein assembly upon ERK signalling. This signalling leads to phosphorylation of the protein LIN28A, which then converges within mRNA hubs with another protein, PABP, to induce selective decay of mRNAs which are no longer needed to maintain pluripotent cell fate. This is required for progression of early development. This is a great example of productive collaboration between the researchers in Ljubljana and London, more from Miha on the paper here.
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.