DEVELOPMENTAL/TISSUE-SPECIFIC EXPRESSION OF NEURAL GENES

BC1 RNA is unique in that it represents the first neural--specific and developmentally regulated non-messenger RNA (transcribed by RNA polymerase) Furthermore recent evidence suggest that BC1 may belong to a novel subclass of genes that, in addition, features elements of RNA polymerase II transcripts. A major portion of the work is geared towards obtaining information concerning the regulation its gene expression in vitro , in cell lines, and in transgenic animals. The genomic environment and chromosomal localization will be studied (both in rodents and in humans) as well as evolutionary and structural aspects of the RNA. Since BC1 is complexed with protein in a ribonucleoprotein particle (RNP), it is planned to isolate the RNP, characterize its protein component(s), partially sequence the polypeptide(s) and clone their cDNAs and genes. Subsequent over-expression in a foreign system will permit the production of antibodies that will aid in the determination of the spatial and temporal distribution of the particle (this work will complement in situ hybridization studies) and, most importantly, will help us to localize the RNP at the subcellular level. This should give us important information pertaining to the function of the BC1 particle. For the same reason, experiments in transgenic mice are planned with the goal of detecting an altered phenotype after functional inactivation of the BC1 gene by the introduction of dominant negative mutations. Furthermore, the isolation of the RNP will permit in vitro testing of its influence on a number of biological processes (e.g. translation). Finally, availability of the human RNP will make it possible to address the question of whether autoantibodies against components of the RNP play a role in any of the neuropsychiatric disorders.