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Age-Dependent Decrease And Alternative Splicing Of Methionine Synthase Mrna In Human Cerebral Cortex And An Accelerated Decrease In Autism, Christina R. Muratore, Nathaniel W. Hodgson, Malav S. Trivedi, Hamid M. Abdolmaleky, Antonio M. Persico, Carla Lintas, Suzanne De La Monte, Richard C. Deth
Age-Dependent Decrease And Alternative Splicing Of Methionine Synthase Mrna In Human Cerebral Cortex And An Accelerated Decrease In Autism, Christina R. Muratore, Nathaniel W. Hodgson, Malav S. Trivedi, Hamid M. Abdolmaleky, Antonio M. Persico, Carla Lintas, Suzanne De La Monte, Richard C. Deth
Richard Deth
The folate and vitamin B12-dependent enzyme methionine synthase (MS) is highly sensitive to cellular oxidative status, and lower MS activity increases production of the antioxidant glutathione, while simultaneously decreasing more than 200 methylation reactions, broadly affecting metabolic activity. MS mRNA levels in postmortem human cortex from subjects across the lifespan were measured and a dramatic progressive biphasic decrease of more than 400-fold from 28 weeks of gestation to 84 years was observed. Further analysis revealed alternative splicing of MS mRNA, including deletion of folate-binding domain exons and age-dependent deletion of exons from the cap domain, which protects vitamin B12 (cobalamin) …