Human Catechol- O -Methyltransferase Haplotypes Modulate Protein Expression by Altering mRNA Secondary Structure
University of North Carolina at Chapel Hill · National Institutes of Health · +3 more institutions
Abstract
Catechol-O-methyltransferase (COMT) is a key regulator of pain perception, cognitive function, and affective mood. Three common haplotypes of the human COMT gene, divergent in two synonymous and one nonsynonymous position, code for differences in COMT enzymatic activity and are associated with pain sensitivity. Haplotypes divergent in synonymous changes exhibited the largest difference in COMT enzymatic activity, due to a reduced amount of translated protein. The major COMT haplotypes varied with respect to messenger RNA local stem-loop structures, such that the most stable structure was associated with the lowest protein levels and enzymatic activity. Site-directed mutagenesis that eliminated the stable…
Citation impact
- FWCI
- 18.91
- Percentile
- 100%
- References
- 20
Authors
8- AGAndrea G. Nackley
University of North Carolina at Chapel Hill, National Institutes of Health, Research Triangle Park Foundation, Attagene, National Center for Biotechnology Information
- SASvetlana A. Shabalina
University of North Carolina at Chapel Hill, National Institutes of Health, Research Triangle Park Foundation, Attagene, National Center for Biotechnology Information
- IEInna E. Tchivileva
University of North Carolina at Chapel Hill, National Institutes of Health, Research Triangle Park Foundation, Attagene, National Center for Biotechnology Information
- KSKathryn Satterfield
University of North Carolina at Chapel Hill, National Institutes of Health, Research Triangle Park Foundation, Attagene, National Center for Biotechnology Information
- OKOlexandr Korchynskyi
University of North Carolina at Chapel Hill, National Institutes of Health, Research Triangle Park Foundation, Attagene, National Center for Biotechnology Information
Topics & keywords
- Haplotype
- Nonsynonymous substitution
- Biology
- Catechol-O-methyl transferase
- Genetics
- Mutagenesis
- Methyltransferase
- Gene