Our new preprint highlights how premature transcription termination in yeast tightly controls the expression of a potentially toxic protein. A fantastic collaboration with the labs of Peter Swain and Michael Duchen and spearheaded by Sofia Esteban Serna!
Over the past few years we and others have produced a large number of proteomics datasets that revealed many putative RNA-binding proteins (RBPs).
However, it was unclear from our data what fraction of these putative RBPs were genuine RNA-binders.
Therefore, to enhance the experimental data, we developed pyRBDome, a comprehensive pipeline that enables users to identify putative RNA-binding regions within proteins and perform statistical analysis to determine if peptides identified in these proteomics studies are indeed bona-fide RNA-binding regions.
Liang-Cui, Niki and Hugh, together with many honour and MSc students, spent the last three years building a powerful pipeline for identifying RNA-binding residues in putative RNA-binding proteins.
In collaboration with Prof. Atlanta Cook, Prof, David Dockrell and Dr. Douglas Houston, we recently were awarded a 5 year Medical Research Council Programme grant to continue our research on Helix-Turn-Helix proteins and their association with RNA in Staphylococcus aureus.
We are currently looking for two talented post-docs wishing to join our team in 2024!
Our Wellcome Trust iCM PhD student Sofia Esteban Serna attended the 2022 Brittish Yeast meeting.
She presented her work on what we believe is a new mechanism for co-transcriptionally regulating noise in gene expression during stress responses.
From the Microbiology Society Website:
"British Yeast Group 2022: From Genomes to Cells took place on 7–9 September 2022 and was held at the University College London, UK.
Our S. aureus (MRSA) RNA interactome papers (2x!) have been published in Nature Communications!!!
Using CLASH we unearthed large RNA-RNA interaction networks in this pathogenic and antibiotic resistant bacterium.
Together with Jai Tree's group we identified interactions between non-coding RNAs and mRNAs that regulate (1) tolerance of vancomycin, our last-line antibiotic for battling MRSA, and (2) the production of cytolytic toxins that enable MRSA to survive and even thrive in the hostile host environment.
Using two very different but highly complementary high-throughput approaches we unearthed the RNA-binding proteome in two clinically-relevant Staphylococcus aureus strains.
We show that our data is highly enriched for metabolic enzymes, in particular those with Rossmann folds.
Moreover, we find that many HTH domain transcription factors also bind RNA, suggesting that they also play a global role in post-transcriptional regulation.
We demonstrate that the CcpA transcription factor also uses HTH domain sequences to bind dsRNA with comparable affinities.
Our paper describing novel algorithms for the detection of RNA structural changes in high-throughput sequencing data has been accepted by Genome Biology!
This project was in close collaboration with Guido Sanguinetti's group and the analyses were performed by two students that at the time were undergraduate students doing internships!
A fantastic result!
The FEBS Journal asked us to write a review early last year and Niki (my PhD student) spent several months doing literature research during the lockdown.
The abstract of the review is below.
Sofia Esteban Serna joins our lab!
Sofia is a new Wellcome Trust iCM PhD student in our lab and her project involves understanding the role of RNA-binding proteins in tight regulation of gene expression.
When some genes are expressed at too high levels it can be toxic to the cell. We found a mechanisn that involves RNA-binding proteins that suppresses this overshooting and keeps tight control of expression of some stress-responsive genes.
Sofia's goal will be to dissect this mechanism and understand how it contributes to stress adaptation.
