Regulated RNA processing provides an important developmental mechanism that contributes to the diversity of products expressed within the nervous system. For a growing number of genes, of which the calcitonin/alpha-CGRP gene is a prototypic example, there is a distinct pre-mRNA processing pathway in the CNS. Little is known of the molecular mechanisms which regulate this neural-specific RNA processing. However, the observation that mRNA transcripts expressed from a single gene can be differentially processed in distinct cell types necessarily implies that factors that mediate pre-mRNA processing events are different in different tissues. Because small nuclear ribonucleoproteins (snRNPs) are known participants in pre-mRNA splicing events, cell specific variants of their component polypeptides or snRNAs are good candidates for factors which regulate alternative splicing. An example of a tissue-specific snRNP component which may be associated with alterative processing is the snRNP protein called N which is highly abundant in the brain. It is also likely that sequences within genes play roles in targeting transcripts to particular processing pathways. In this proposal we outline a series of experiments to explore both the sequences within gene transcripts crucial for neural specific alterative pre-mRNA processing events, and the potential regulation of these events by cell-specific snRNPs.
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