Analysis of A-to-I RNA Editing in Schizophrenia Risk Gene MIR137
Public Deposited- Last Modified
- February 26, 2019
- Creator
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Pudukodu, Harish
- Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
- Abstract
- Schizophrenia is a complex psychiatric disorder that likely emerges as a result of interacting genetic and environmental risk factors. A prominent hypothesis for the etiology of schizophrenia is that schizophrenia emerges as a result of pre- and/or perinatal viral infection-induced inflammation in genetically predisposed individuals. This gene-environment interaction may be mediated by genetic regulators such as microRNA 137 (miR137), a regulatory RNA with a set of related SNPs that is highly associated with schizophrenia, and epigenetic phenomena such as RNA editing, which has been previously associated with schizophrenia and infection. Here I interrogate this gene-environment interaction by quantifying RNA editing of miR137, assessing the functional impact of this editing, and predicting its effects on schizophrenia risk in conjunction with a risk SNP. High-throughput RNA sequencing coupled to the PrimerID methodology revealed that miR137 is edited at a statistically significant level (p < 0.05) in both fetal human brain and adult mouse brain. Site-directed mutagenesis and luciferase assays demonstrated that A-to-I modification of certain pertinent bases in miR137 impart a large decrease in affinity to a target sequence. Finally, mathematical modeling and simulations based on empirical findings suggest that this RNA editing and a MIR137 schizophrenia-risk SNP significantly modulate inflammation-based schizophrenia risk burden (p < 2 x 10-16). These findings demonstrate that infection, the MIR137 gene, and RNA editing likely interact to promote schizophrenia risk, and thus this study serves to elucidate the cooperative influences of genetic and environmental risk factors on schizophrenia.
- Date of publication
- autumn 2016
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- DOI
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- Rights statement
- In Copyright
- Note
- Funding: CSURF (Office of Undergraduate Research)
- Advisor
- Ball, Louise
- Degree
- Bachelor of Science in Public Health
- Honors level
- Honors
- Degree granting institution
- University of North Carolina at Chapel Hill
- Extent
- 37 p.
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