The human DNA-binding protein, PO-GA, is homologous to the large subunit of mouse replication factor C: regulation by alternate 3' processing of mRNA.
We have previously cloned a human gene encoding a 128-kDa protein which we termed PO-GA [Lu et al., Biochem. Biophys. Res. Commun. 193 (1993) 779-786]. In the present report, we compared PO-GA to recent DNA database entries and determined that PO-GA was 80% identical, at the amino-acid level, to the large subunit of replication factor C (activator 1) cloned from mouse [Burbelo et al., Proc. Natl. Acad. Sci. USA 91 (1994) in press]. This indicates that PO-GA probably represents the corresponding subunit of human replication factor C. In addition, PO-GA has high homology to a putative Drosophila transcription factor. All three proteins contain a nuclear translocation signal and an ATP/ADP-binding motif, and are highly conserved in regions with homology to Escherichia coli and yeast DNA ligases. We determined that PO-GA mRNA species of 5.3 and 4.5 kb can be detected in most human tissues, but levels are especially high in ovary. Analysis of the sequence of a new PO-GA cDNA clone that we obtained reveals a previously undetected 650-bp 3'-UTR extension. This region contains several A+U-rich regions potentially involved in regulation of mRNA stability. This fragment only hybridizes to the larger 5.3-kb mRNA. Comparison of cDNA sequences revealed that the two mRNA species arise as a result of alternate use of poly(A)-addition sites. Since the ratio of the two mRNA species is variable in different tissues, we speculate that alternative 3' processing of the PO-GA mRNA is utilized as a mechanism of regulating cellular levels of mRNA.
Lu
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Department of Pharmacology, Georgetown University, Washington, DC 20007.
Riegel
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics*; D018398:Homeodomain Proteins; D006801:Humans; D051379:Mice; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D011061:Poly A / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014157:Transcription Factors
C096816:BCL2-related protein A1; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C096063:MATA1 protein, S cerevisiae; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; C081632:RFC1 protein, human; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D011061:Poly A; D051818:Replication Protein C