| Literature DB >> 23912948 |
Georg Stoll1, Olli P H Pietiläinen2,3,4, Bastian Linder1, Jaana Suvisaari5, Cornelia Brosi1, William Hennah3,5, Virpi Leppä3, Minna Torniainen5, Samuli Ripatti2,3, Sirpa Ala-Mello6, Oliver Plöttner7, Karola Rehnström2, Annamari Tuulio-Henriksson5, Teppo Varilo3,4, Jonna Tallila2, Kati Kristiansson3, Matti Isohanni8, Jaakko Kaprio3,5,9, Johan G Eriksson10,11,12,13,14, Olli T Raitakari15,16, Terho Lehtimäki17, Marjo-Riitta Jarvelin18,19,20,21, Veikko Salomaa22, Matthew Hurles2, Hreinn Stefansson23, Leena Peltonen2,3,4,24, Patrick F Sullivan25, Tiina Paunio3,4,26, Jouko Lönnqvist5,6, Mark J Daly27,28, Utz Fischer1, Nelson B Freimer29, Aarno Palotie2,3,28.
Abstract
Implicating particular genes in the generation of complex brain and behavior phenotypes requires multiple lines of evidence. The rarity of most high-impact genetic variants typically precludes the possibility of accruing statistical evidence that they are associated with a given trait. We found that the enrichment of a rare chromosome 22q11.22 deletion in a recently expanded Northern Finnish sub-isolate enabled the detection of association between TOP3B and both schizophrenia and cognitive impairment. Biochemical analysis of TOP3β revealed that this topoisomerase was a component of cytosolic messenger ribonucleoproteins (mRNPs) and was catalytically active on RNA. The recruitment of TOP3β to mRNPs was independent of RNA cis-elements and was coupled to the co-recruitment of FMRP, the disease gene product in fragile X mental retardation syndrome. Our results indicate a previously unknown role for TOP3β in mRNA metabolism and suggest that it is involved in neurodevelopmental disorders.Entities:
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Year: 2013 PMID： 23912948 PMCID： PMC3986889 DOI： 10.1038/nn.3484
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 24.884