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Title: Characterisation and function of nuclear RNA at mitosis in mammalian cells
Author: El-Messeiry, Sarah Mamduh Ibrahim
ISNI:       0000 0004 7963 1306
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2019
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The nuclear membrane encloses DNA, nuclear RNAs and proteins separating them from the surrounding cytoplasm but breaks down at the onset of mitosis allowing spindle attachment to the highly condensed mitotic chromosomes. Interphase nuclei contain a tremendous amount of RNA, and the prevailing view is that it mostly diffuses to the cytoplasm at mitosis and is inactive while there. However, using FISH and de novo RNA labelling, I found significant populations of formerly nuclear RNA to be immediately encircling and also embedded between mammalian mitotic chromosomes. These patterns were distinct from the RNA component of the perichromosomal layer (i.e. pre-rRNA) and conserved between different cell lines, and so reveal a previously unrecognised subcellular zone. The consistent patterns and large amounts of RNA involved suggested they would have essential functions at mitosis. In support of that idea, I found that globally suppressing de novo RNA transcription, but not protein synthesis, caused major mitotic aberration including failure of NMBD, loss of chromatid definition and failure to progress through mitosis. To analyse this further, I developed a novel chromosome decondensation assay based on isolated mitotic prometaphase clusters in which simple changes in Mg2+ concentration could induce dramatic and reversible decondensation. Remarkably, and contrary to all current models of mitotic chromosome condensation, I showed that RNA embedded in the cluster was the primary determinant of the degree of chromosome decondensation. These novel findings introduce RNA as a key player in mitotic chromosomal condensation, chromosome segregation and nuclear membrane break down. Also, opening up a new frontier in understanding mitotic division.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral