Polyadenylate Polymerase (PAP) and 3' End pre-mRNA Processing: Function, Assays, and Association with Disease

Abstract

Polyadenylate polymerase (PAP) is one of the enzymes involved in the formation of the polyadenylate tail of the 3' end of mRNA. Poly (A) tail formation is a significant component of 3' processing, a link in the chain of events, including transcription, splicing, and cleavage/polyadenylation of pre-mRNA. Transcription, capping, splicing, polyadenylation, and transport take place as coupled processes that can regulate one another. The poly(A) tail is found in almost all eukaryotic mRNA and is important in enhancing translation initiation and determining mRNA stability. Control of poly(A) tail synthesis could possibly be a key regulatory step in gene expression. PAP-specific activity values are measured by a highly sensitive assays and immunocytochemical methods. High levels of PAP activity are associated with rapidly proliferating cells, it also prevents apoptosis. Changes of PAP activity may cause a decrease in the rate of polyadenylation in the brain during epileptic seizures. Testis-specific PAP may play an important role in spermiogenesis. PAP was found to be an unfavorable prognostic factor in leukemia and breast cancer. Furthermore, measurements of PAP activity may contribute to the definition of the biological profile of tumor cells. It is crucial to know the specific target causing the elevation of serum PAP, for it to be used as a marker for disease. This review summarizes the recently accumulated knowledge on PAP including its function, assays, and association with various human diseases, and proposes future avenues for research.