Alternative polyadenylation of poly(A) binding protein nuclear 1 (PABPN1) mRNA

Abstract

Polyadenylation is a 3' end RNA processing event that contributes to the regulation of gene expression by affecting turnover, stability, export, and translation of mRNA. Approximately 53 % of all human genes have multiple polyadenylation sites (PAS). Regulation at the level of alternative polyadenylation has begun to be investigated, but still requires much more elucidation.Bioinformatics has identified unique alternative polyadenylation of a polyadenylation factor mRNA, poly (A) binding protein nuclear 1 (PABPN1). The mRNAs of this polyadenylation factor contains multiple polyadenylation sites.Two polyadenylation signals were found for the PABPN1 mRNA. The proximal PAS is predicted from bioinformatics to be the strong polyadenylation site. The distal PAS was suggested to be a weaker site. However, we found the distal PAS contains putative novel auxiliary upstream polyadenylation elements. There are two G‐rich elements found in the upstream region of PABPN1 mRNA that are very highly conserved, suggestive of important function. Mutations of these two G‐rich elements seem to exhibit opposing effects on polyadenylation.Previous studies from other labs have shown that G‐rich elements located downstream of polyadenylation sites enhance cleavage, and affect polyadenylation signal usage, but remains unexplored when upstream. Research supported by NIH and the Foundation of UMDNJ grants.