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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 that fine-tune the workings of a cell.

We study how RNA networks regulate gene expression in cells. RNAs are coated by proteins to form ribonucleoprotein complexes (RNPs). These proteins guide the RNA on its journey through the cell, while the RNAs also regulate the functions of bound proteins. To understand how these interactions contribute to cellular functions, we develop new techniques that reveal protein-RNA and RNA-RNA interactions within cells.

In particular, we want to understand how RNPs contribute to the function of nerve cells in development, or their degeneration in disease. We investigate how faulty RNPs lead to conditions affecting the nervous system, particularly neurodegenerative diseases such as amyotrophic lateral sclerosis, and how changes in RNPs contributed to brain evolution. We hope our discoveries will open up opportunities to develop new RNA-based therapies.

Dementia Research Institute at KCL

​​We are currently part of the Department of Neuromuscular Diseases at the UCL Queen Square Institute of Neurology, and in April 2022 we will join the Dementia Research Institute at King's College London.

Francis Crick Institute London

Ule Lab is seconded to the Francis Crick Institute until Feb 2025

Institute of Chemistry Ljubljana Slovenia

An ERC grant, co-hosted at the Ljubljana Chemistry Institute, funds a satellite lab at the institute since 2020.

New publication

Hallegger et al, TDP-43 condensation properties specify its RNA-binding and regulatory repertoire Cell. 2021 Sep 2;184(18).

We addressed the long-standing question of how TDP-43 condensation influences its RNA binding specificity. We created variants of TDP-43 with a gradient of condensation properties as evident by phase separation in vitro, foci formation and RNA binding and regulation in cells. Led by Martina Hallegger, Anob Chakrabarti and Flora Lee, and with fantastic collaborators from Jim Shorter's lab and our Ljubljana satellite, as well as Nick Fawzi, Rickie Patani and Nick Luscombe. 

We exploited the full potential of comparative iCLIP to find that the condensation capacity of TDP-43 is required for efficient binding to long RNA regions with widely dispersed UG-rich motifs. We refer to such molecular-scale assemblies as ‘binding region condensates’. Condensation is also required for TDP-43 regulation of a subset of its target 3’UTR isoforms, including autoregulation of TDP-43 itself. Such selective deregulation might contribute to the early stages of neurodegenerative diseases that involve TDP-43. More from Martina on Twitter.

A free CLIP analysis pipeline and web platform

With Luscombe lab and collaborators, we co-developed a Nextflow analysis pipeline and a web server iMaps for streamlined analysis of CLIP data, which is freely available for general use. Read more about it here

 

iMaps can be used to obtain public CLIP data, to analyse unpublished data in a secure manner, and to share your data publicly upon publication. Read more about its documentation and tutorial. A new iMaps site is in preparation, which will be fully based on the Nextflow pipeline and both its front- and back-end will be open access. It will contain many new and interactive functionalities, and will become fully operational in September (at that point, data will also be seamlessly transferred from old to new iMaps). Current iMaps can be used till then, and public data is available at both sites.

Recently published methods

iiCLIPAn 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.

UltraplexSoftware 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.

Ribocutter: A streamlined Cas9-based protocol for removing abundant rRNA/ncRNA contaminants from Ribo-seq, CLIP or other small RNA-seq libraries and a software tool for designing ready-to-order sgRNA templates.

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.

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.

Moving soon!

On 1/4/22, the lab will move from UCL to the KCL, where Jernej will take the position of UK DRI Centre Director at KCL. Most of the lab will gradually transition from the Crick institute, while 3 members will remain for longer as a a satellite lab in the Crick.