title: Complete human NF1 cDNA sequence: two alternatively spliced mRNAs and absence of expression in a neuroblastoma line.
abstract: Neurofibromatosis type 1 (NF1) is caused by mutations in a large gene on chromosome 17q11.2. Previously described partial cDNAs for this gene predicted a protein related to yeast IRA1/IRA2 and the mammalian RAS GTPase activator protein GAP. To initiate a detailed study of the role of this gene in NF1, we have characterized a set of overlapping cDNAs that represent its complete coding sequence. Our results show that two differentially expressed human NF1 mRNAs differ by a 63-bp insertion in the GAP-related domain. These mRNAs predict two 2,818- and 2,839-amino acid proteins with calculated molecular masses of approximately 317 and 319 kD. Extensive similarity to IRA proteins is evident in a 1,450-amino-acid central segment, roughly between amino acids 900 and 2,350. However, the remainder of the NF1 protein is not significantly similar to other proteins. Interestingly, the SK-N-SH human neuroblastoma line expresses no detectable NF1 mRNA, indicating that expression of NF1 is not essential for viability of this neural crest-derived tumor cell line.
authors.affiliation: Massachusetts General Hospital Cancer Center, Charlestown 02129.
authors.forename: A
authors.initials: A
authors.lastname: Bernards
authors.forename: V H
authors.initials: VH
authors.lastname: Haase
authors.forename: A E
authors.initials: AE
authors.lastname: Murthy
authors.forename: A
authors.initials: A
authors.lastname: Menon
authors.forename: G E
authors.initials: GE
authors.lastname: Hannigan
authors.forename: J F
authors.initials: JF
authors.lastname: Gusella
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA; D015870:Gene Expression; D016514:Genes, Neurofibromatosis 1; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009447:Neuroblastoma / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D004247:DNA