High Degree of NCAM Diversity Generated by Alternative RNA Splicing in Brain and Muscle

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Abstract
The neural cell adhesion molecules (NCAMs) are cell surface glycoproteins involved in vertebrate cell contact formation. Several NCAM mRNA types are generated from a single primary transcript by alternative splicing and differential polyadenylation. In this presentation we analyse sequence heterogeneities within NCAM transcripts detected in the junctions of exons 7/8, 12/13 and 13/14. The highest degree of evolutionary conservation is observed in the 30-nucleotide insertion (π) between exons 7 and 8, coding for an identical peptide sequence in the mouse, rat and chicken. The most complex splicing pattern is found between exons 12 and 13, called splice site a. Three alternative exons of 15, 48 and 42 nucleotides can be inserted in various combinations, which may also contain the additional trinucleotide AAG. In mouse muscle cell lines, differential ‘extra exon’ and AAG usage in splice site α creates up to 16 NCAM diversity forms, some (if not all) of which are also expressed in mouse brain. Additional microdiversity is generated by the insertion of an alternative AAG trinucleotide in exon junction 13/14. If all combinations of splicing patterns identified so far were to occur and to be translated, there could be up to 192 different NCAM proteins.