Alternative first exon splicing regulates subcellular distribution of methionine sulfoxide reductases.

Article Details

Citation

Copy to clipboard

Kim HY, Gladyshev VN

Alternative first exon splicing regulates subcellular distribution of methionine sulfoxide reductases.

BMC Mol Biol. 2006 Mar 16;7:11.

PubMed ID

16542431 [ View in PubMed

]

Abstract

BACKGROUND: Methionine sulfoxide reduction is an important protein repair pathway that protects against oxidative stress, controls protein function and has a role in regulation of aging. There are two enzymes that reduce stereospecifically oxidized methionine residues: MsrA (methionine-S-sulfoxide reductase) and MsrB (methionine-R-sulfoxide reductase). In many organisms, these enzymes are targeted to various cellular compartments. In mammals, a single MsrA gene is known, however, its product is present in cytosol, nucleus, and mitochondria. In contrast, three mammalian MsrB genes have been identified whose products are located in different cellular compartments. RESULTS: In the present study, we identified and characterized alternatively spliced forms of mammalian MsrA. In addition to the previously known variant containing an N-terminal mitochondrial signal peptide and distributed between mitochondria and cytosol, a second mouse and human form was detected in silico. This form, MsrA(S), was generated using an alternative first exon. MsrA(S) was enzymatically active and was present in cytosol and nucleus in transfected cells, but occurred below detection limits in tested mouse tissues. The third alternative form lacked the active site and could not be functional. In addition, we found that mitochondrial and cytosolic forms of both MsrA and MsrB in Drosophila could be generated by alternative first exon splicing. CONCLUSION: Our data suggest conservation of alternative splicing to regulate subcellular distribution of methionine sulfoxide reductases.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Methionine	Methionine-R-sulfoxide reductase B1	Protein	Humans	Unknown	Substrate	Details