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 coordinate the development and function of nerve cells. We also investigate how changes in RNPs contributed to brain evolution, and how faulty RNPs lead to conditions affecting the nervous system, such as amyotrophic lateral sclerosis. We hope our discoveries will open up opportunities to develop new RNA-based therapies.
Strittmatter et al, psiCLIP reveals dynamic RNA binding by DEAH-box helicases before and after exon ligation. Nat Commun. 2021 Mar 5;12(1):1488.
After a fruitful collaboration with the Kiyoshi Nagai lab we bring you psiCLIP - a method for profiling helicase-RNA contacts in defined spliceosome states. Led by Lisa Strittmatter & Charlotte Capitanchik, and with fantastic insights from Sebastian Fica.
Studies of spliceosomal interactions are challenging due to their dynamic nature. We have previously established spliceosome iCLIP to map spliceosome engagement with pre-messenger RNAs in human cell lines. We now present a variant applicable to purified spliceosome: psiCLIP (purified spliceosome individual nucleotide resolution Cross-Linking and ImmunoPrecipitation), which involves first stalling and purifying the spliceosome at specific stages. Thereby, we investigate how Prp16 and Prp22 engage their RNA substrate at defined points in the splicing pathway. The wet-lab method is accompanied by an open source bioinformatics pipeline written in Snakemake https://github.com/luslab/psiclip. Read more about it in the LMB news.
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.
A journey through RNA space and time
We will organise a hybrid symposium on transcriptomic approaches to study protein-RNA complexes. Originally planned for Saturday 21st August, we decided to delay due to the current surge in Covid cases in UK, but watch this space for a new date.
Held at the National Institute of Chemistry, Ljubljana, Slovenia, the symposium will bring together our London and Ljubljana teams, as well as several invited speakers. We plan to have up to 50 in-person and 300 online participants, so if interested, do register here.