We plan to study the principles of gene regulation in the nervous tissue, emphasizing RNA and its processing. In particular, the unusual poly(A)- mRNA which only in the brain has a high complexity and which is developmentally regulated will be analyzed via individual cDNA clones. A second line of experiments involves small brain-specific RNA with an initial stress on BCl RNA which has homologies to a repetitive Alu-like element, the identifier (ID) sequence. The outlined research will give insights into the structure, processing, developmental pattern and anatomical location of the poly(A)- RNAs. Indirectly, we will be able to deduce the protein coding sequences of these RNAs and test the presence of the polypeptides with antibodies to synthetic peptides as well as to gain from the protein structure some insight on their possible role in the nervous tissue. The genes of these RNAs will be studied with respect to common elements (e.g., common 3' processing sites or pomoter regions that regulate the timed levels of expression in development), the absence of introns, and possible relationships within gene families. Experiments on the second project, concerning brain specific small RNAs, will yield information on whether the non-ID part of the BCl RNA is heterologous, or consists mainly of A-residues. In that case we shall proceed directly to determine whether the RNA is part of a small cytoplasmic ribonucleoprotein complex (scRNP). If the remainder of the sequence is unique we shall also isolate the gene for the BCl RNA and examine its structure. Our studies might lead to future experiments focussing on the subcellular location and function of the particle. Furthermore, the possible role of BCl scRNP-antibodies in autoimmune diseases could be studied. In general, studying molecules which are specific to the brain might lead to the discovery of principles which are unique to that organ and which might give us insights in some of the mechanisms concerning memory, behavior, aging and mental diseases at the molecular level.
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