TISSUE-SPECIFIC ALTERNATIVE SPLICING OF NEUROFIBROMATOSIS-1 (NF1) MESSENGER-RNA

The neurofibromatosis 1 gene NF1 appears to play a crucial role in reg ulating the proliferation of cells of neural crest origin. The NF1 gen e is a 300 kbp gene, encoding a complex pattern of mRNA related to the presence or absence of two alternative splices. The first splice, in the centre of the coding region of the gene, results in the addition o f 63 bp in the GAP-related domain. The second splice located 4203 bp d ownstream. near the 3' terminus of the coding region of the gene, cons ists of a 54 bp insert. RT-PCR analysis demonstrates that the most pre valent splice variant in human tissues is the one which contains the G AP-related splice and omits the 3' terminal splice. It is also the for m expressed in the peripheral nerve, adrenal medulla, benign NF1 neuro fibromas and NF1 neurosarcomas. Conversely, a few organs (brain, muscl e) exhibit extensive alternative splicing leading to the co-expression of four distinct transcripts. The reproducibility of the relative lev els of each of the splice types in the different organs indicates a ti ssue-specific splicing pattern of the NF1 gene.