polyadenylation

Polyadenylation is the addition of a poly(A) tail to the 3' end of RNA molecules, most commonly the mature messenger RNA in eukaryotes. It occurs in the nucleus after transcription, as part of mRNA 3' end processing, and is essential for mRNA stability, export from the nucleus, and translation.

The process is directed by a polyadenylation signal, typically the sequence AAUAAA, located upstream of the cleavage site. Cleavage and polyadenylation are carried out by a multi-protein machinery that includes cleavage and polyadenylation specificity factor (CPSF), the cleavage stimulation factor (CstF), and additional factors such as CFIm and CFII_m. An endonuclease (often CPSF73) cleaves the transcript at the cleavage site, after which poly(A) polymerase adds adenosine residues to form the tail. In mammals, poly(A) tail length is regulated by nuclear poly(A)-binding protein PABPN1 and generally ranges around a few dozen to several hundred nucleotides. The tail is subsequently bound by poly(A)-binding proteins, which influence stability, nuclear export, and translation efficiency.

Polyadenylation affects mRNA fate in multiple ways. The poly(A) tail protects transcripts from exonucleolytic decay, promotes export to the cytoplasm, and enhances translation initiation. Alternative polyadenylation (APA) generates mRNA isoforms with different 3' untranslated regions, altering regulatory element content and gene expression.

Exceptions and variations exist: most histone mRNAs are not polyadenylated and instead use a unique stem-loop structure for processing; mitochondrial and some viral RNAs may exhibit distinct polyadenylation features.