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.
We’ve recently established the web server iMaps for streamlined analysis of CLIP data, which is freely available for general use. iMaps can be used to analyse unpublished data in a secure manner, and to obtain and visualise public CLIP data.