Structure and dynamics of the mammalian cell nucleus

Group leader: Judith Sleeman

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.

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Related links

Research group website

Publications

Sleeman, J 2013, ' Small nuclear RNAs and mRNAs: linking RNA processing and transport to spinal muscular atrophy ' Biochemical Society Transactions , vol 41, no. 4, pp. 871-875.

Overview

Scientists associated with the thirty-two research groups that are affiliated with the Biomedical Sciences Research Complex perform highly innovative, multi-disciplinary research in eleven broad areas of biomedical research, employing state-of-the-art techniques to address key questions at the leading edge of the biomedical and biological sciences.

Follow the links on the left to view individual research groups associated with one or more of the eleven BSRC research areas.

Research areas

Scientists associated with the thirty-two research groups that are affiliated with the Biomedical Sciences Research Complex perform highly innovative, multi-disciplinary research in eleven broad areas of biomedical research, employing state-of-the-art techniques to address key questions at the leading edge of the biomedical and biological sciences.

Follow the links on the left to view individual research groups associated with one or more of the eleven BSRC research areas.

Research by academic schools

Research in the BSRC is conducted by thirty-two independent research groups based in the Schools of Biology, Chemistry, Physics and Astronomy, and Medicine. Follow the links on the left to view groups associated with each school.