Tissue-specific alternative splicing of neurofibromatosis 1 (NF1) mRNA

The neurofibromatosis 1 gene NF1 appears to play a crucial role in regulating the proliferation of cells of neural crest origin. The NF1 gene 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 of 63 bp in the GAP-related domain. The second splice located 4203 bp downstream, near the 3' terminus of the coding region of the gene, consists of a 54 bp insert. RT-PCR analysis demonstrates that the most prevalent splice variant in human tissues is the one which contains the GAP-related splice and omits the 3' terminal splice. It is also the form expressed in the peripheral nerve, adrenal medulla, benign NF1 neurofibromas and NF1 neurosarcomas. Conversely, a few organs (brain, muscle) exhibit extensive alternative splicing leading to the co-expression of four distinct transcripts. The reproducibility of the relative levels of each of the splice types in the different organs indicates a tissue-specific splicing pattern of the NF1 gene.