Genetic and biochemical evidence that RNA binding protein, TOP3b, may be a common factor in schizophrenia, autism spectrum disorders, and intellectual impairment is reported by two papers published this week in Nature Neuroscience. Taken together with prior findings that schizophrenia and autism may share common genetic risk factors, these studies identify potential biological processes that may be related to the cognitive deficits shared by these disorders.
Due to migration patterns over the centuries, a region in Northern Finland has a high incidence of schizophrenia. By studying this population, Nelson Freimer, Utz Fischer and colleagues found that some of these individuals carry a small deletion in their genomes that includes the gene TOP3b and that this mutation increases the risk for cognitive impairment and schizophrenia.
In an independent study, Weidong Wang, Sige Zou and colleagues report that the TOP3b protein binds to and unwinds RNA and that this process depends on interactions with another RNA binding protein, FMRP. The gene encoding the FRMP protein is mutated in Fragile X syndrome, a disorder that often includes the presence of intellectual disability and autism. Wang and Zou’s team also showed that many of the RNAs bound by FMRP were also bound by TOP3b and that similar to mutations in FMRP, mutations of TOP3b caused abnormal synapse development in flies and mice.