Title |
Deletion of TOP3β, a component of FMRP-containing mRNPs, contributes to neurodevelopmental disorders
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Published in |
Nature Neuroscience, August 2013
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DOI | 10.1038/nn.3484 |
Pubmed ID | |
Authors |
Georg Stoll, Olli P H Pietiläinen, Bastian Linder, Jaana Suvisaari, Cornelia Brosi, William Hennah, Virpi Leppä, Minna Torniainen, Samuli Ripatti, Sirpa Ala-Mello, Oliver Plöttner, Karola Rehnström, Annamari Tuulio-Henriksson, Teppo Varilo, Jonna Tallila, Kati Kristiansson, Matti Isohanni, Jaakko Kaprio, Johan G Eriksson, Olli T Raitakari, Terho Lehtimäki, Marjo-Riitta Jarvelin, Veikko Salomaa, Matthew Hurles, Hreinn Stefansson, Leena Peltonen, Patrick F Sullivan, Tiina Paunio, Jouko Lönnqvist, Mark J Daly, Utz Fischer, Nelson B Freimer, Aarno Palotie |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United Kingdom | 5 | 25% |
United States | 4 | 20% |
United Arab Emirates | 1 | 5% |
Unknown | 10 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 10 | 50% |
Scientists | 6 | 30% |
Science communicators (journalists, bloggers, editors) | 4 | 20% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | 1% |
Netherlands | 2 | <1% |
Germany | 2 | <1% |
Italy | 1 | <1% |
Brazil | 1 | <1% |
United Kingdom | 1 | <1% |
Finland | 1 | <1% |
Japan | 1 | <1% |
China | 1 | <1% |
Other | 0 | 0% |
Unknown | 237 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 62 | 25% |
Student > Ph. D. Student | 47 | 19% |
Student > Master | 22 | 9% |
Student > Bachelor | 21 | 8% |
Student > Doctoral Student | 13 | 5% |
Other | 47 | 19% |
Unknown | 38 | 15% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 71 | 28% |
Medicine and Dentistry | 40 | 16% |
Biochemistry, Genetics and Molecular Biology | 34 | 14% |
Neuroscience | 19 | 8% |
Psychology | 12 | 5% |
Other | 22 | 9% |
Unknown | 52 | 21% |