Human Catechol-O-Methyltransferase Haplotypes Modulate Protein Expression by Altering mRNA Secondary Structure
Top Cited Papers
- 22 December 2006
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 314 (5807) , 1930-1933
- https://doi.org/10.1126/science.1131262
Abstract
Catechol-O-methyltransferase (COMT) is a key regulator of pain perception, cognitive function, and affective mood. Three common haplotypes of the humanCOMTgene, 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 majorCOMThaplotypes 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 structure restored the amount of translated protein. These data highlight the functional significance of synonymous variations and suggest the importance of haplotypes over single-nucleotide polymorphisms for analysis of genetic variations.Keywords
This publication has 20 references indexed in Scilit:
- A periodic pattern of mRNA secondary structure created by the genetic codeNucleic Acids Research, 2006
- Analysis of internal loops within the RNA secondary structure in almost quadratic timeBioinformatics, 2006
- Distribution of the strength of selection against amino acid replacements in human proteinsHuman Molecular Genetics, 2005
- The Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene may influence morphine requirements in cancer pain patientsPain, 2005
- Genetic basis for individual variations in pain perception and the development of a chronic pain conditionHuman Molecular Genetics, 2004
- Genetics of human prefrontal functionBrain Research Reviews, 2003
- COMT
val
158
met
Genotype Affects µ-Opioid Neurotransmitter Responses to a Pain StressorScience, 2003
- Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptorHuman Molecular Genetics, 2003
- Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structureJournal of Molecular Biology, 1999
- Specifie codon usage pattern and its implications on the secondary structure of silk fibroin mRNAJournal of Molecular Biology, 1988