Alternative splicing generates two forms of mRNA coding for human heparin-binding growth factor 1.
Human class 1 heparin-binding growth factor (HBGF-1), also known as acidic fibroblast growth factor, is a mitogen for a variety of mesoderm- and neutroectoderm-derived cells in vitro as well as an angiogenic factor in vivo. Several oncogenes and growth factors have been shown to be homologous to HBGF-1. Four cDNA clones coding for HBGF-1 have been isolated from a human brain stem cDNA library. Nucleotide sequence analysis revealed that alternative splicing generated at least two different forms of HBGF-1 mRNA. Because the difference occurs in the 5'-untranslated regions, these transcripts may result from the usage of alternative promoters. One of the cDNA clones contains the polyadenylation signal, AATAAA, and a poly(A) tail, representing the 3'-end of an HBGF-1 mRNA. RNAase protection assays suggested this cDNA clone corresponds to a minor transcript, and the majority of the HBGF-1 mRNA terminates at 3.1 kbp downstream from the translation termination codon. The biological significance of this unusually long 3'-untranslated sequence is not known. To study the HBGF-1 gene structure, we have isolated 50 kbp of contiguous genomic DNA coding for the HBGF-1 protein. Both restriction enzyme mapping and nucleotide sequencing established that the distance between the first and second protein-coding exons is 13.6 kbp while that between the second and third is 5.3 kbp. By using the HBGF-1 cDNA as a probe, we showed that human fetal heart expresses high levels of HBGF-1 mRNA. Thus, HBGF-1 may be involved in mediating processes such as embryonic development and vascular growth in the heart.
Department of Internal Medicine, Ohio State University, Columbus 43210.
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Chiu
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Wang
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Lehtoma
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005091:Exons; D005318:Fetal Heart / Q000378:metabolism; D016220:Fibroblast Growth Factor 1; D006133:Growth Substances / Q000235:genetics* / Q000378:metabolism; D006493:Heparin / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D012326:RNA Splicing; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D006133:Growth Substances; D012333:RNA, Messenger; D016220:Fibroblast Growth Factor 1; D006493:Heparin; D004247:DNA