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Mischo Lab

The Mischo Lab studies how gene expression can be controlled through the modulation of transcription termination.

Gene expression patterns are classically thought to be decided at the level of messenger (m)RNA transcription initiation. However, in budding yeast, mRNA fate and therefore gene expression is equally affected by the choice of different transcription termination mechanisms. Influenza A virus (IAV) inhibits host-mRNA transcription termination, which blocks changes to gene expression and so counteracts cellular antiviral defence-mechanisms.  Using both IAV infected cells and budding yeast, we investigate how the modulation of transcription termination activity is used to enhance the plasticity of our transcriptome from yeast to man.

Members

Stuart McKellar

Stuart McKellar

Postdoctoral Research Associate

Hannah Mischo

Hannah Mischo

Sir Henry Dale Fellow

Blue Car stopping at STOP sign and red, virus infected car, failing to recognise STOP signal.

Host-Virus-Interactions to regulate Gene Expression through the modulation of Transcription Termination

Cellular infection with Influenza A (IAV) and Herpes Simplex (HSV1) Virus leads to profound transcription termination defects in the host cell. Some IAV strains utilise their effector protein NS1 to inhibit transcription termination, but NS1 independent pathways have evolved in other IAV strains. Intrigued by the observation that two completely unrelated viruses rely on the inhibition of the same cellular process, we will examine which mechanisms evolved to inhibit host cell transcription termination and test if these contribute to viral survival. Using biochemistry, transcriptomics, genetics, cell biology, structural and molecular biology, we will also scrutinize how cells react to viral interference with basic transcription termination.

Red and blue yeast cell on seesaw – transcription products change in red versus blue conditions.

Molecular Mechanisms to modulate Cleavage and Polyadenylation

In budding yeast, S. cerevisiae, RNA polymerase II terminates transcription by use of two different protein complexes, as well as by DNA-binding proteins that may act as transcriptional roadblocks. Each of these different termination pathways impacts in different ways on the fate of the resulting mRNA. For example, changes in nutrient status can cause suppression of one termination complex in favour of another (red versus blue in the pictogram), which may result in the generation of non-exported and consequently non-translated mRNA molecules. This project will exploit the great amenability of S. cerevisiae as a tractable biochemical and genetic model system. We will identify the molecular mechanisms that alter the activity of termination factors and consequently provoke global gene expression changes. Due to high interspecies conservation of the canonical RNA polymerase II termination and RNA processing mechanisms, we anticipate that our findings in yeast will be mirrored or conserved in mammalian cells.

View all publications
  • Sir Henry Dale Fellowship

PhD students in the Mischo Lab:

Our partners

Wellcome trust

Wellcome Trust

Royal soc

Royal Society

Contact us

+44 (0) 207 848 9605