David Tollervey

RNA processing and quality control.

David Tollervey studied for a BSc in Microbiology in Edinburgh and then for a PhD in Genetics at Cambridge in the lab of Herb Arst. He then moved to the University of California, San Francisco, as a postdoctoral fellow in the laboratory of Christine Guthrie. In 1983 he relocated to a permanent post at the Institut Pasteur in Paris, which he left in 1988 to move to the European Molecular Biology Laboratory (EMBL) in Heidelberg as a group leader. He returned to Edinburgh in 1997 as Professor of RNA Biology and a Wellcome Trust Principal Research Fellow.

From 2011 to 2021 he served as Director of the Wellcome Centre for Cell Biology. He is a Fellow of the Royal Society, the Royal Society of Edinburgh, the Academy of Medical Science and Academia Europaea, a member of EMBO and Past President of the international RNA Society.

portrait photo of David Tollervey
David Tollervey

The aim of the Tollervey group is to understand the pathways that process newly transcribed RNAs and assemble RNA-protein complexes, the mechanisms that regulate these pathways and the surveillance activities that monitor their fidelity. They are currently determining how these processes change dynamically, particularly in disease-related model systems and following stress.

Katie Bexley, Alexandria DiGiacomo, Sophie Giguere, Aziz El Hage, Aleksandra (Ola) Helwak, Alexandra Lehmann, Jule Nieken, Elisabeth Petfalski, Johanna Seidler, Thomas Tan and Pin Tong.


RNA-protein interactions have important functions at all steps in gene expression, including transcription, RNA processing and mRNA translation. RNA defects underpin many genetic diseases, while responses to environmental stress are frequently mediated by altered RNA-protein interactions. Over recent years we have made good progress in understanding stress responses in yeast and have started to apply these insights in human cells. We have also applied our techniques to understand the molecular basis of RNA-linked disease, and this report will focus on these advances.

Coronavirus infection involves a complex pathway of coding and non-coding RNA synthesis. To better understand the biology of viral gene expression and replication we generated constructs for studying RNA interactions by viral proteins. We then followied host and viral RNA metabolism and RNA-protein interactions over detailed time courses during infection. This is giving insights into the timing and regulation of viral RNA replication and virus-host interactions (Bresson et al. 2025).

Transcription elongation is stochastic, driven by a Brownian ratchet, making it subject to changes in velocity. On the rDNA, multiple polymerases are linked by “torsional entrainment”, generated by DNA rotation. We reported that release of entrainment, by co-transcriptional 3’-end cleavage, is permissive for relative movement between polymerases, promoting pausing and backtracking (Petfalski et al. 2025). Subsequent termination (polymerase release) is facilitated by the 5’-exonuclease Rat1 (Xrn2) and backtracked transcript cleavage by RNAPI subunit Rpa12. These activities are reproduced in vitro. Short nascent transcripts close to the transcriptional start site, combined with nascent transcript folding energy, similarly facilitate RNAPI pausing. Nascent, backtracked transcripts at pause sites, are terminated by forward and reverse “torpedoes”; Rat1 and exosome cofactor TRAMP. Topoisomerase 2 localizes adjacent to RNAPI pause sites, potentially allowing continued elongation by downstream polymerases. Mathematical modelling supported substantial premature termination. These basic insights into transcription in vivo, will be relevant to many systems.

Organisms must constantly cope with variable and stressful environments. This problem is especially acute for unicellular organisms such as the budding yeast Saccharomyces cerevisiae, but human cells must also frequently respond to diverse stresses. Cells respond to stress by altering protein expression at both the transcriptional and translational levels, and RNA-binding proteins (RBPs) are at the heart of stress adaptation. Yeast growing in glucose medium utilize aerobic fermentation, generating ATP only from glycolysis. Following glucose withdrawal, very rapid translational silencing is driven by a specialized metabolic mechanism (Bexeley et al. 2025). Intracellular NTP levels drop drastically over 30 sec, before stabilizing at a regulated, post-stress set-point. Programmed translational control results from the differential NTP affinities of key enzymes; ATP falls below the (high) binding constants for DEAD-box helicase initiation factors, including eIF4A, driving mRNA release and blocking 80S assembly. Contrastingly, GTP levels always greatly exceed the (low) binding constants for elongation factors, allowing ribosome run-off and orderly translation shutdown. Translation initiation is immediately lost on all pre-existing mRNAs, before being preferentially re-established on newly synthesized, upregulated stress-response transcripts (Figure 1). We conclude that enzymatic constants are tuned for metabolic remodelling, allowing hierarchical inhibition of energy-consuming processes on very rapid timescales. Aerobic fermentation has evolved repeatedly, and is also seen in human cells. These results are therefore potentially relevant to many systems.


figure showing levels of RNA

Bexley, K., Ristová, M., Sharma, S. Spanos, C., Chabes, A. and Tollervey, D. (2025) Metabolic tuning enables immediate adaptation to energy stress in yeast. Mol Cell. 85, 3623-3639.

Turowski, T.W., Petfalski, E., Winz, W.-L. and Tollervey, D. (2025) Multiple mechanisms of termination modulate the dynamics of RNAPI transcription. Cell Rep. 25,115325

Bresson, S., Sani, E., Armatowska, A., Dixon, C., and Tollervey, D. (2025) The transcriptional and translational landscape of HCoV-OC43 infection. PLoS Pathogens, 21, e1012831..


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