Polyadenylerings

Polyadenylerings, or polyadenylation, is the enzymatic addition of a poly(A) tail to the 3’ end of pre‑messenger RNA (pre‑mRNA) molecules during eukaryotic gene expression. The process begins around 30 nucleotides downstream of the transcriptional cleavage site, where the cleavage and polyadenylation specificity factor (CPSF) recognizes the AAUAAA hexamer motif. After endonucleolytic cleavage of the nascent transcript, poly(A) polymerase (PAP) adds up to 200 adenosine monophosphate residues to the 3’ end. The poly(A) tail is then bound by poly(A) binding proteins (PABPs) which protect the RNA from exonucleases and promote efficient translation.

The poly(A) tail influences RNA stability, nuclear export, translation initiation, and degradation. Cells regulate the length of the tail through feedback between PAP activity and PABPs, and alternative polyadenylation can generate mRNA isoforms that differ in their 3’ untranslated regions, affecting post‑transcriptional regulation.

Impaired polyadenylation is implicated in various diseases. Mutations in CPSF or PAP that reduce poly(A) tail length can cause neurodevelopmental defects, while aberrant alternative polyadenylation is frequently observed in cancers, leading to oncogene activation or tumor suppressor silencing.

Experimental techniques used to study polyadenylation include 3’ rapid amplification of cDNA ends (3’ RACE), poly(A) tail length assays such as poly(A) test (PAT), and next‑generation sequencing methods designed to capture poly(A) sites (3’ end sequencing). Bioinformatic analyses of polyadenylation site databases provide insight into regulatory motifs and evolutionary conservation across species.