Structural organization of the human reduced folate carrier gene: evidence for 5' heterogeneity in lymphoblast mRNA.
The reduced folate carrier (rfc1) gene encodes a protein that is involved in the intracellular accumulation of folates. Point mutations in this gene and alterations resulting in the down regulation of its message are major factors involved in the resistance to antifolate chemotherapeutic compounds. As a framework for understanding the significance of such changes in relation to gene expression and function, in this report we describe the organization of the rfc gene from human lymphoblasts. The gene contains 5 exons (2 to 6) coding for protein. At least four 5' exons, used in a mutually exclusive manner in the production of the rfc message from lymphoblast cells, are spliced to exon 2, which contains the translational start site. "Semi-quantitative" PCR indicates that exon 1 is preferentially used. The major transcriptional start site has been mapped by RACE and RNase protection to a region 109 to 135 base pairs 5' to the start of exon 1. The 5' region of the gene has no TATA box-like sequence but contains several consensus binding sites for transcriptional factors such as SP-1, MZF1, CREB, AP-1, ETS, GATA-1 and GATA-2. The overall organization of the human gene is similar to that of the hamster and mouse genes.
Williams
F M
FM
Department of Microbiology and Immunology, University of Western Ontario, London, Canada.
Flintoff
W F
WF
D017398:Alternative Splicing; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005091:Exons; D005796:Genes / Q000235:genetics*; D006801:Humans; D007438:Introns; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D058978:Reduced Folate Carrier Protein; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
D002352:Carrier Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; C120043:SLC19A2 protein, human; C548700:Slc19a1 protein, mouse; C492292:Slc19a2 protein, mouse; D004247:DNA