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Title: The fate of nonsense-mediated RNA decay factors and their substrates during neuronal differentiation
Author: Almasoudi, Kholoud S.
ISNI:       0000 0004 7425 8223
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2018
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Nonsense-mediated mRNA decay (NMD) is a quality control mechanism that recognises and degrades mRNA transcripts that harbour premature termination codons. It has been shown that NMD has also a regulatory role for gene expression. This is particularly critical for embryonic and brain development. Autism, schizophrenia and intellectual disability have all been linked to mutations in the NMD factor UPF3B. This project aims to examine the expression levels of the NMD factors including UPF1, UPF2, UPF3B, SMG1, and SMG5 during the in vitro differentiation of neural stem cells into neurons, astrocytes or oligodendrocytes, and to link this to changes in overall gene expression. The expression of NMD factors were analysed at the protein level by western blot and the RNA level by RT-qPCR and RNA-Seq analysis. My data show a strong downregulation of UPF1, UPF2 and UPF3B at the protein level during the differentiation of neural stem cells into the three cell types. However, the mRNA levels for genes encoding these factors did not show a corresponding change. I tested whether the NMD factor UPF1 is targeted at the post-translational level through the cellular protein degradation pathways; ubiquitin-proteasome pathway or lysosomal proteolysis. My results show a possible role for the lysosomal proteolysis in UPF1 protein control. RNA-Seq analysis has shown that many mRNAs from genes that are known NMD targets are not affected by the reduction of UPF1, UPF2and UPF3b proteins. A few genes with a variety of functions however are affected and have increased RNA levels. This work contributes towards the understanding of the role of NMD in neuronal differentiation.
Supervisor: Müller, Berndt Sponsor: Saudi Arabia Ministry of Education
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Messenger RNA ; Gene expression ; Mutation (Biology) ; Embryology