dependencies among editing sites in serotonin 2c receptor mrna之间的依赖关系编辑网站5 -羟色胺2 c受体信使rna.pdfVIP

Dependencies among Editing Sites in Serotonin 2C Receptor mRNA 1 2 3,4 Liran Carmel , Eugene V. Koonin , Stella Dracheva * 1 Department of Genetics, The Alexander Silberman Institute of Life Sciences, Faculty of Science, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, Israel, 2 National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America, 3 James J Peters Veterans Affairs Medical Center, Bronx, New York, United States of America, 4 Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, United States of America Abstract The serotonin 2C receptor (5-HT2CR)–a key regulator of diverse neurological processes–exhibits functional variability derived from editing of its pre-mRNA by site-specific adenosine deamination (A-to-I pre-mRNA editing) in five distinct sites. Here we describe a statistical technique that was developed for analysis of the dependencies among the editing states of the five sites. The statistical significance of the observed correlations was estimated by comparing editing patterns in multiple individuals. For both human and rat 5-HT2CR, the editing states of the physically proximal sites A and B were found to be strongly dependent. In contrast, the editing states of sites C and D, which are also physically close, seem not to be directly dependent but instead are linked through the dependencies on sites A and B, respectively. We observed pronounced differences between the editing patterns in humans and rats: in humans site A is the key determinant of the editing state of the other sites, whereas in rats this role belongs to site B. The structure of the dependencies among the editing