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

Abstract

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.