Investigating the potential regulation of Asic2 by microRNAs

Cole, Hannah Rebecca (2012) Investigating the potential regulation of Asic2 by microRNAs. Masters thesis, University of East Anglia.

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Abstract

Multiple Sclerosis (MS) is an inflammatory disease which causes neurodegeneration. It is a disease which affects mainly young adults, and symptoms become more aggressive over time. It is thought that mutations in a variety of genes may be a large contributor to the development of MS. Many Linkage and Genome Wide Association Studies have been performed to find genes which may be mis-expressed among different sections of the world’s population. Through one of these Genome Wide Associations a Single Nucleotide Polymorphism (SNP) was found in the 3’ UTR of the ACCN1 gene. This gene codes for Acid Sensing Ion Channel 2, a major ion channel predominantly found in cells within the Central Nervous System (CNS). As this channel is closely connected to systems in the CNS which are known to be affected in patients with MS, it was thought that the SNP should be investigated further. As the SNP was found in the 3’ UTR it was suggested that miRNAs may play a role. This study took on this suggestion and investigated the possibility of ACCN1 being controlled by a miRNA and whether this control was in any way affected by the SNP found.
The initial experiment found that of the two variants, rs28936A was controlled more strongly by a miRNA than the variant rs28936G. Resequencing of the samples showed a further three SNPs in the same region. Several miRNA target sites were predicted that contained at least one of the SNPs, however none of these could be validated experimentally using luciferase essays. The three SNPs were tested individually using the same luciferase experiment but none were found to have a more significant effect over luciferase expression over the others. The results therefore indicate that all SNPs contribute to the reduction in miRNA binding. Further research is proposed to investigate in more detail, potential miRNA candidates. It was concluded from these results that the ACCN1 gene is being controlled by an unknown miRNA via binding to the 3’UTR, that the rs28936A variant is more strongly controlled by the miRNA and that of all SNPs found (including the two originals and three ‘new’ SNPs) none have a significantly stronger miRNA control than the other.

Item Type:	Thesis (Masters)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Megan Ruddock
Date Deposited:	04 Mar 2014 15:04
Last Modified:	04 Mar 2014 15:04
URI:	https://ueaeprints.uea.ac.uk/id/eprint/47890
DOI:

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