
<ArticleTitle>A novel nuclear human <prot>poly(A) polymerase</prot> (<prot>PAP</prot>), <prot>PAP gamma</prot>.</ArticleTitle>
<AbstractText><prot>Poly(A) polymerase</prot> (<prot>PAP</prot>) is present in multiple forms in mammalian cells and tissues. Here we show that the 90-kDa isoform is the product of the gene <prot>PAPOLG</prot>, which is distinct from the previously identified genes for <prot>poly(A) polymerase</prot>s. The 90-kDa isoform is referred to as human <prot>PAP gamma</prot> (<prot>hsPAP gamma</prot>). <prot>hsPAP gamma</prot> shares 60% identity to human <prot>PAPII</prot> (<prot>hsPAPII</prot>) at the amino acid level. <prot>hsPAP gamma</prot> exhibits fundamental properties of a bona fide <prot>poly(A) polymerase</prot>, specificity for ATP, and cleavage and polyadenylation specificity factor/hexanucleotide-dependent polyadenylation activity. The catalytic parameters indicate similar catalytic efficiency to that of <prot>hsPAPII</prot>. Mutational analysis and sequence comparison revealed that <prot>hsPAP gamma</prot> and <prot>hsPAPII</prot> have similar organization of structural and functional domains. <prot>hsPAP gamma</prot> contains a <prot>U1A protein</prot>-interacting region in its C terminus, and <prot>PAP gamma</prot> activity can be inhibited, as <prot>hsPAPII</prot>, by the <prot>U1A protein</prot>. <prot>hsPAPgamma</prot> is restricted to the nucleus as revealed by in situ staining and by transfection experiments. Based on this and previous studies, it is obvious that multiple isoforms of <prot>PAP</prot> are generated by three distinct mechanisms: gene duplication, alternative RNA processing, and post-translational modification. The exclusive nuclear localization of <prot>hsPAP gamma</prot> establishes that multiple forms of <prot>PAP</prot> are unevenly distributed in the cell, implying specialized roles for the various isoforms.</AbstractText>
