Dr Judith Sleeman:
Senior Lecturer in Cell and Developmental Biology

Research Overview:

The mammalian cell nucleus has a highly ordered structure. The detailed organisation of the nucleus and how this affects its function are not fully understood. Essential to the expression, or functioning, of genes are ‘transcription’ of the DNA instructions into a messenger RNA (mRNA) intermediate and ‘translation’ of this into the protein ‘product’ of the gene. Almost all mammalian genes contain introns, which are sequences represented in the DNA but not in the protein. These must be removed, or ‘spliced’, from the mRNA message before it can be translated. The accuracy of mRNA splicing is essential for correct gene expression. snRNPs (small nuclear ribonucleoproteins) are essential splicing factors and show a complex pattern of distribution within the nucleus. They localise to a number of nuclear domains including speckles and Cajal bodies. The formation of snRNPs is a complex process. Early steps occur outside the nucleus in the cytoplasm, and require a protein called Survival of Motor Neurons (SMN). Insufficient expression of SMN is responsible for the inherited neurodegenerative disease, spinal muscular atrophy (SMA). SMN is also found in the nucleus where it concentrates, along with snRNPs, in Cajal bodies. It is not clear how the loss of SMN protein leads to the disease. All cells need to splice their RNA correctly, but SMA specifically affects motor neurons. I am studying the maturation of snRNP splicing factors, with a particular emphasis on their dynamics within the nucleus and differences between neural and non-neural cell types that may be significant for SMA.


5 (of 28 /dk/atira/pure/researchoutput/status/published available) for jes14 (source: University of St Andrews PURE)
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Neurochondrin interacts with the SMN protein suggesting a novel mechanism for Spinal Muscular Atrophy pathology Kim D. Morrison, Sally Lorna Shirran, Ewout J. N. Groen, Tom H. Gillingwater, Catherine Helen Botting, Judith Elizabeth Sleeman
Journal of Cell Science 2018 vol. 131
The Cajal body and the nucleolus Laura Trinkle-Mulcahy, Judith Elizabeth Sleeman
RNA Biology 2017 vol. 14 pp. 739-751
Nuclear bodies Judith Elizabeth Sleeman, Laura Trinkle-Mulcahy
Current Opinion in Cell Biology 2014 vol. 28 pp. 76-83
Time-resolved quantitative proteomics implicates the core snRNP protein SmB together with SMN in neural trafficking Alan R. Prescott, Alecandra Bales, John James, Laura Trinkle-Mulcahy, Judith Elizabeth Sleeman
Journal of Cell Science 2014 vol. 127 pp. 812-827