A novel miRNA cluster within the circadian clock gene NPAS2 and the implications of rs1811399, an autism enriched single nucleotide polymorphism

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This PhD investigated the role of the rs181399 single nucleotide polymorphism (A or C) in the maturation of a previously unknown microRNA. microRNA are potent regulators of gene expression and their expression is finely controlled. Canonically the microRNA processing machinery recognise hairpin-loops of single stranded RNA as a substrate for processing. Mutations, such as rs1811399 can disturb the hairpin leading to reduction in expression. The work presented in this thesis demonstrates that a novel microRNA cluster is located within intron 1 of NPAS2 which is independently transcribed of its host gene. Secondly, plasmid constructs were used to integrate versions of the novel microRNA hairpin containing either an A allele or a C into cell lines. Utilising this method the impact of the C allele was noted to be deleterious to microRNA maturation. RNA protection assays have demonstrated that both precursor microRNA and mature microRNA is constitutively expressed within a multitude of tissue types, seemingly independently of its host gene. The potential impact of the C allele on genetic regulation was analysed bioinformatically by analysing potential gene targets and the pathways they participate in.


Iaith wreiddiolSaesneg
Sefydliad dyfarnu
Goruchwylydd / Goruchwylwyr / Cynghorydd
  • Thomas Caspari (Goruchwylydd)
Noddwyr traethodau hir
  • Knowledge Economy Skills Scholarship (KESS)
Dyddiad dyfarnuIon 2014