A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Deletion of TOP3 beta, a component of FMRP-containing mRNPs, contributes to neurodevelopmental disorders

Julkaisun tekijät: Stoll G, Pietilainen OPH, Linder B, Suvisaari J, Brosi C, Hennah W, Leppa V, Torniainen M, Ripatti S, Ala-Mello S, Plottner O, Rehnstrom K, Tuulio-Henriksson A, Varilo T, Tallila J, Kristiansson K, Isohanni M, Kaprio J, Eriksson JG, Raitakari OT, Lehtimaki T, Jarvelin MR, Salomaa V, Hurles M, Stefansson H, Peltonen L, Sullivan PF, Paunio T, Lonnqvist J, Daly MJ, Fischer U, Freimer NB, Palotie A
Julkaisuvuosi: 2013
Journal: Nature Neuroscience
Tietokannassa oleva lehden nimi: NATURE NEUROSCIENCE
Lehden akronyymi: NAT NEUROSCI
Numero sarjassa: 9
Volyymi: 16
Julkaisunumero: 9
Sivujen määrä: 13
ISSN: 1097-6256

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 TOP3 beta revealed that this topoisomerase was a component of cytosolic messenger ribonucleoproteins (mRNPs) and was catalytically active on RNA. The recruitment of TOP3 beta 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 TOP3 beta in mRNA metabolism and suggest that it is involved in neurodevelopmental disorders.

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