Deletion of TOP3β, a component of FMRP-containing mRNPs, contributes to neurodevelopmental disorders.

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 diseas

SUBMITTER: Stoll G 

PROVIDER: S-EPMC3986889 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature