Nuclear regulation of mRNA stability in response to cellular stress

Exposure to acute stress reduces cell viability or fitness and therefore immediate adaption is crucial for cell survival. Such rapid change of cell physiology requires tight coordination of several levels of gene expression regulation, including synthesis and stability efficiencies of stress-induced mRNA. In the past decade, CTD readers, conserved multifunctional proteins interacting with the RNA Polymerase II (Pol II) C-terminal domain (CTD), have emerged as central players in the coordination of nuclear events in the RNA metabolism and thus, in regulation of gene expression. Thus, the aim of this project is to investigate roles for CTD readers in the regulation of RNA synthesis and turnover in response to cellular stress.
Promoters of stress-induced genes play crucial role in stress response as they force cytoplasmic localization and translation of mRNA in adverse conditions. In contrast to house-keeping genes activated by TFIID, stress-induced gene expression is promoted by the SAGA complex, which modulates chromatin structure, recruits pre-initiation complexes, promotes transcription elongation and mRNA export. Our preliminary analysis has revealed a link between the SAGA complex and CTD reader-dependent nuclear RNA degradation suggesting that transcriptional activators determine the choice of the RNA degradation pathway of the transcribed nascent mRNA. Therefore, the successful student will investigate the connection between SAGA-dependent transcription and nuclear RNA degradation of stress-induced genes in yeast S. cerevisiae. Ultimately, this project will uncover a new pathway, which regulates cellular stress response in eukaryotic cells.

Please find additional funding text below. For further funding details, please see the ‘Funding’ section.
The School of Biosciences offers a number of UK Research Council (e.g. BBSRC, NERC) PhD studentships each year. Fully funded research council studentships are normally only available to UK nationals (or EU nationals resident in the UK) but part-funded studentships may be available to EU applicants resident outside of the UK. The deadline for applications for research council studentships is typically at the end of January each year.

Each year we also have a number of fully funded Darwin Trust Scholarships. These are provided by the Darwin Trust of Edinburgh and are for non-UK students wishing to undertake a PhD in the general area of Molecular Microbiology. The deadline for this scheme is also typically at the end of January each year.

Informal enquiries about the post are strongly encouraged and should be directed to Dr Pawel Grzechnik.