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.
Briese et al. A systems view of spliceosomal assembly and branchpoints with iCLIP. (2019) Nat Struct Mol Biol. 2019 Sep 30
Studies of spliceosomal interactions are challenging due to their dynamic nature. Here we used spliceosome iCLIP, which immunoprecipitates SmB along with small nuclear ribonucleoprotein particles and auxiliary RNA binding proteins, to map spliceosome engagement with pre-messenger RNAs in human cell lines. This revealed seven peaks of spliceosomal crosslinking around branchpoints (BPs) and splice sites. We identified RNA binding proteins that crosslink to each peak, including known and candidate splicing factors. Moreover, we detected the use of over 40,000 BPs with strong sequence consensus and structural accessibility, which align well to nearby crosslinking peaks. We show how the position and strength of BPs affect the crosslinking patterns of spliceosomal factors, which bind more efficiently upstream of strong or proximally located BPs and downstream of weak or distally located BPs. These insights exemplify spliceosome iCLIP as a broadly applicable method for transcriptomic studies of splicing mechanisms.
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.