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PhD Studentship: Understanding the Role that RNA Helicase UPF1 Plays in Nuclear Processes of Gene Expression

University of Birmingham - School of Biosciences

Qualification Type: PhD
Location: Birmingham
Funding for: UK Students, EU Students, International Students
Funding amount: MIBTP FUNDED PROJECT
Hours: Full Time
Placed On: 27th November 2023
Closes: 4th January 2024

Accurate gene expression is crucial for the survival of all life forms. RNA helicases are a large class of enzymes involved at the multiple stages of the process, including transcription, pre-mRNA processing and translation. UPF1 is one of these enzymes and is conserved in all eukaryotes. Until recently it was understood that UPF1 primarily operates during translation and nonsense mediated mRNA decay (NMD) in the cytoplasm (1), however we recently reported that UPF1 is constantly shuttling between nucleus and cytoplasm. Crucially, our observations show that UPF1 associates with nascent pre-mRNA transcripts and that it plays genome-wide roles in nuclear RNA-based processes – including Pol II transcription and mRNA export - in evolutionary divergent organisms (2-3). These observations change our understanding of the roles of UPF1 in gene expression. They also change current ideas of how this protein might prevent/modifies neurodegenerative diseases such as amyloid lateral sclerosis (ALS). Specifically, we have discovered that depletion of UPF1 leads to nuclear accumulation of RNA aggregates, one of the hallmarks of neurodegeneration. With this project we aim to understand the molecular mechanism of this RNA aggregation in Drosophila models of ALS as well as understanding the import role/s of UPF1 in eukaryotic cells.

Funding notes:

MIBTP FUNDED PROJECT

You can apply for funding under the MIBTP doctoral training programme of the BBSRC available via the School of Biosciences, University of Birmingham, for both UK and international applicants. DEADLINE FOR MIBTP STUDENTSHIPS IS 4 JANUARY 2024

Our project is within: "Understanding the rules of life" and "Integrated understanding of health". This project will be supervised by Dr Saverio Brogna (s.brogna@bham.ac.uk).

OTHER FUNDING OPPORTUNITIES

You can also apply with other sources of funding. For example, you could apply for a scholarship from your own country.

References:

1. Brogna, S., McLeod, T. and Petric, M. (2016). The Meaning of NMD: Translate or Perish. Trends in Genetics, 32(7), pp.395-407.

2. Singh, A., Choudhury, S., De, S., Zhang, J., Kissane, S., Dwivedi, V., Ramanathan, P., Petric, M., Orsini, L., Hebenstreit, D. and Brogna, S. (2019). The RNA helicase UPF1 associates with mRNAs co-transcriptionally and is required for the release of mRNAs from gene loci. eLife, 8, e41444.

3. De, S et al. Genome-wide chromosomal association of Upf1 is linked to Pol II transcription in Schizosaccharomyces pombe, Nucleic Acids Research, Volume 50, Issue 1, 11 350–367.

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