Deletion of TOP3ß, a component of FMRP-containing mRNPs, contributes to neurodevelopmental disorders.
Nat Neurosci
; 16(9): 1228-1237, 2013 Sep.
Article
em En
| MEDLINE
| ID: mdl-23912948
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 TOP3ß revealed that this topoisomerase was a component of cytosolic messenger ribonucleoproteins (mRNPs) and was catalytically active on RNA. The recruitment of TOP3ß 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 TOP3ß in mRNA metabolism and suggest that it is involved in neurodevelopmental disorders.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Esquizofrenia
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Anormalidades Múltiplas
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Deleção de Sequência
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Transtornos Cognitivos
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DNA Topoisomerases Tipo I
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Síndrome de DiGeorge
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
Nat Neurosci
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Alemanha