Two different promoters direct expression of two distinct forms of mRNAs of human platelet‐activating factor receptor

Abstract

The human platelet-activating factor (PAF) receptor gene exists as a single copy on chromosome 1. We identified two 5'-noncoding exons, each of which has distinct transcriptional initiation sites. These exons are alternatively spliced to a common splice acceptor site on a third exon that contains the total open reading frame to yield two different species of functional mRNA (Transcript 1 and 2). Transcript 1 has consensus sequences for transcription factor NF-KB and Sp-1, and the Initiator (mr) sequence. homologous to the murine terminal deoxynucleotidyltransferase gene. Transcript 2 also contains consensus sequences for transcription factor AP-1, AP-2, and Sp-1. Transcripts 1 and 2 were both detected in heart, lung, spleen, and kidney, whereas only Transcript 1 was found in peripheral leukocytes, a differentiated human eosinophilic cell line (EoL-1 cells), and brain. Existence of distinct promoters was thus suggested to play a role in the regulatory control of PAF receptor gene expression in different human tissues and cells.

The Human CC Chemokine Receptor 5 (CCR5) Gene

“…4. Interestingly, as is the case for the promoters for CXCR2 (18) and platelet-activating factor receptor gene (22,23), the two CCR5 promoters are also tandemly arranged on the gene. Another feature that is common to both CCR5 and CXCR2 is that they contain exon-exon units that are uninterrupted by an intron.…”

“…Since alternative splicing in the 5Ј-UTRs appears to be a feature common to several human chemokine and chemoattractant receptors (18,22,24), we hypothesized that this might also be true for CCR5. To test this hypothesis, we designed a strategy that involved 5Ј-RACE and RT-PCR techniques, and probed the diversity in the CCR5 mRNA structure in several primary human cell types and the human cell lines THP-1 and Jurkat.…”

“…Two such GPCR clusters are members of the chemokine receptor subclass, and receptors for the classical chemoattractants, such as the N-formyl peptide receptor. To date, the complete mRNA and genomic organization of only a limited number of human chemokine receptors has been described (16 -20), however, a comparison of their structural organization with that of the receptors for the classical chemottractants reveals some striking similarities (21)(22)(23)(24). 1) Their ORFs are usually intronless or contain a single intron interrupting the amino-terminal coding region, as is the case for the C5a receptor (21).…”

Characterization of the mouse prostaglandin F receptor gene: a transgenic mouse study of a regulatory region that controls its expression in the stomach and kidney but not in the ovary

“…This type of organization of gene structure seems to be highly conserved among prostanoid receptor genes (Nüsing et al 1993;Hirata et al 1994;Båtshake et al 1995;Arakawa et al 1996); particularly regarding the location of the intron in the sixth transmembrane region, which is observed in every prostanoid receptor gene. This intron, which is not seen in the platelet activating factor (PAF) receptor gene (Mutoh et al 1993), seems to have been conserved in prostanoid receptor genes. In human PAF receptor genes, tissue specific forms of mRNA are expressed by alternative promoter usage (Mutoh et al 1993).…”

“…This intron, which is not seen in the platelet activating factor (PAF) receptor gene (Mutoh et al 1993), seems to have been conserved in prostanoid receptor genes. In human PAF receptor genes, tissue specific forms of mRNA are expressed by alternative promoter usage (Mutoh et al 1993). Although multiple sites for transcription initiation have been shown in the FP gene, the diversity of its initiation appeared to be identical among tissues (Fig.…”