THE HUMAN DNA-BINDING PROTEIN, PO-GA, IS HOMOLOGOUS TO THE LARGE SUBUNIT OF MOUSE REPLICATION FACTOR-C - REGULATION BY ALTERNATE 3' PROCESSING OF MESSENGER-RNA

We have previously cloned a human gene encoding a 128-kDa protein whic h 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 dat abase entries and determined that PO-GA was 80% identical, at the amin o-acid level, to the large subunit of replication factor C (activator 1) cloned from mouse [Burbelo et al., Proc. Natl. Acad. Sci. USA 91 (1 994) in press]. This indicates that PO-GA probably represents the corr esponding subunit of human replication factor C. In addition, PC-GA ha s high homology to a putative Drosophila transcription factor. All thr ee proteins contain a nuclear translocation signal and an ATP/ADP-bind ing motif, and are highly conserved in regions with homology to Escher ichia coli and yeast DNA ligases, We determined that PO-GA mRNA specie s 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 potential ly involved in regulation of mRNA stability. This fragment only hybrid izes 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 t he PO-GA mRNA is utilized as a mechanism of regulating cellular levels of mRNA.