A novel isoform of the neurofibromatosis type-1 mRNA and a switch of isoforms during murine cell differentiation and proliferation.
Four types of cDNAs encoding the GTPase-activating protein-related domain (GRD) of the mouse neurofibromatosis type-1 gene (NF1) have been cloned. One of these isoforms was a newly identified form termed type IV. Analysis of the genomic structure of the mouse NF1-GRD revealed two exons (23A and 23B) between exons 23 and 24, leading to the production of four types of NF1-GRD cDNAs by an alternative splicing mechanism. Amino-acid sequences encoded by NF1-GRD are highly conserved between human and mouse. Analysis of the expression of these transcripts in various tissues of adult mouse revealed that the type-I transcript is predominantly expressed in neural tissues such as brain and spinal cord. Other forms, termed types II, III and IV, are also expressed in various tissues. The type-I and type-II transcripts are expressed equivalently in undifferentiated P19 mouse teratocarcinoma cells, whereas type-I expression becomes predominant during neuronal differentiation by retinoic acid treatment. Expression of type I is also shown to be correlated with cessation of cell proliferation in P19 cells, but not in NIH3T3 cells. These, together with other results, suggest that the four types of NF1-GRD transcripts generated by alternative splicing have some important biological roles in cell differentiation and proliferation.
Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Japan.
A
A
Mantani
S
S
Wakasugi
Y
Y
Yokota
K
K
Abe
Y
Y
Ushio
K
K
Yamamura
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics*; D002455:Cell Division / Q000235:genetics*; D004247:DNA; D016514:Genes, Neurofibromatosis 1; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D004247:DNA