| First Author | Stoll G | Year | 2013 |
| Journal | Nat Neurosci | Volume | 16 |
| Issue | 9 | Pages | 1228-1237 |
| PubMed ID | 23912948 | Mgi Jnum | J:203882 |
| Mgi Id | MGI:5528959 | Doi | 10.1038/nn.3484 |
| Citation | Stoll G, et al. (2013) Deletion of TOP3beta, a component of FMRP-containing mRNPs, contributes to neurodevelopmental disorders. Nat Neurosci 16(9):1228-37 |
| abstractText | 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 TOP3beta revealed that this topoisomerase was a component of cytosolic messenger ribonucleoproteins (mRNPs) and was catalytically active on RNA. The recruitment of TOP3beta 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 TOP3beta in mRNA metabolism and suggest that it is involved in neurodevelopmental disorders. |
