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Updated: May 30, 2026
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In vitro tRNA Methylation Assay with the Entamoeba histolytica DNA and tRNA Methyltransferase Dnmt2 (Ehmeth) Enzyme
Published on: October 19, 2010
Methionine adenosyltransferase 2A/2B and methylation: gene sequence variation and functional genomics
Kendra K S Nordgren1, Yi Peng, Linda L Pelleymounter
1Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Summary
Genetic variations in methionine adenosyltransferase (MAT) genes (MAT2A and MAT2B) were identified. Some MAT2A variants impact enzyme activity, and gene expression is linked to specific SNPs, paving the way for pharmacogenomic studies.
Area of Science:
- Biochemistry and Molecular Biology
- Genetics and Genomics
- Pharmacogenomics
Background:
- Methionine adenosyltransferase (MAT) enzymes are crucial for synthesizing S-adenosylmethionine, the primary biological methyl donor.
- Mammals express distinct MAT isoforms encoded by MAT1A (liver) and MAT2A (nonhepatic) genes, with MAT2B encoding a regulatory protein.
Purpose of the Study:
- To identify and characterize genetic polymorphisms in the MAT2A and MAT2B genes.
- To investigate the functional impact of identified polymorphisms on MAT enzyme activity and expression.
Main Methods:
- Resequencing of MAT2A and MAT2B exons, splice junctions, and flanking regions in 288 DNA samples from three ethnic groups.
- Imputation of additional single nucleotide polymorphisms (SNPs) using 1000 Genomes Project data.
- Functional genomic studies in COS-1 cells and mRNA expression analysis in lymphoblastoid cells.
Main Results:
- Identified 74 polymorphisms in MAT2A, including two nonsynonymous SNPs; the Val11 MAT2A variant showed reduced enzyme activity and protein levels.
- Identified 44 polymorphisms in MAT2B, with two nonsynonymous SNPs showing no significant protein alteration.
- Imputation identified thousands of additional polymorphisms for both genes. Coexpression of MAT2A and MAT2B increased enzyme activity. Significant associations were found between SNPs and mRNA expression levels for both genes.
Conclusions:
- Genetic variations in MAT2A and MAT2B are common and can influence enzyme function and expression.
- The identified polymorphisms and their functional effects provide a basis for future pharmacogenomic research into MAT2A/2B.
- These findings support further investigation into the clinical relevance of MAT gene variations in personalized medicine.
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