title: Gene structure, localization and role in oxidative stress of methionine sulfoxide reductase A (MSRA) in the monkey retina.
abstract: MSRA (EC 1.8.4.6) is a member of the methionine sulfoxide reductase family that can reduce methionine sulfoxide (MetO) in proteins. This repair function has been shown to protect cells against oxidative damage. In this study we have assembled the complete gene structure of msrA and identified the presence of two distinct putative promoters that generate three different transcripts. These transcripts were cloned by 5'RACE and code for three MSRA isoforms with different N-termini. The different forms of MSRA target to distinct intracellular regions. The main MSRA transcript (msrA1) had been previously shown to target the mitochondria. MsrA2 and 3 originate from a second promoter and target the cytosol and nuclei. In the monkey retina msrA message was detected mainly in the macular RPE-choroid region while its activity was measured mainly in the soluble fractions of fractionated neural retina and RPE-choroid. The MSRA protein is found throughout the retina but is especially abundant at the photoreceptor synapses, ganglion and Müller cells. Interestingly, MSRA was not detected in the mitochondria of the photoreceptor inner segments. The RPE in the peripheral retina shows very low levels of expression but the RPE in the macular region is strongly labeled. Targeted silencing of msrA message rendered cultured RPE cells more sensitive to oxidative damage suggesting a role for MSRA in RPE protection against oxidative stress. Collectively these data suggest MSRA may play an important role in protecting macular RPE from oxidative damage.
authors.affiliation: Lab of Retinal Cell and Molecular Biology, Mechanisms of Retinal Diseases Section, National Eye Institute, NIH, 7 Memorial drive MSC 0706, Bethesda, MD 20892, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Lee
authors.forename: N V
authors.initials: NV
authors.lastname: Gordiyenko
authors.forename: M
authors.initials: M
authors.lastname: Marchetti
authors.forename: N
authors.initials: N
authors.lastname: Tserentsoodol
authors.forename: D
authors.initials: D
authors.lastname: Sagher
authors.forename: S
authors.initials: S
authors.lastname: Alam
authors.forename: H
authors.initials: H
authors.lastname: Weissbach
authors.forename: M
authors.initials: M
authors.lastname: Kantorow
authors.forename: I R
authors.initials: IR
authors.lastname: Rodriguez
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016923:Cell Death; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D008253:Macaca mulatta / Q000378:metabolism*; D008266:Macula Lutea / Q000201:enzymology; D051150:Methionine Sulfoxide Reductases; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D018384:Oxidative Stress / Q000502:physiology*; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D012160:Retina / Q000201:enzymology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016415:Sequence Alignment; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase