mRNA Formation: 3′‐End

Abstract Eukaryotic mRNAs are derived from precursors synthesised by RNA polymerase II. For 3′‐end formation, precursors are cleaved by an endonuclease, and a poly(A) tail is added. This processing reaction depends on signals in the pre‐mRNA, among them the ‘polyadenylation signal’ AAUAAA. Cleavage and polyadenylation are carried out by a multiprotein complex comprising, in yeast, a minimum of 13 polypeptides, many of which recognise RNA sequence motifs around the polyadenylation site. 3′‐end processing is coupled to transcription. Alternative polyadenylation, that is cleavage and polyadenylation of a precursor RNA at any of several sites, is widespread. The choice of polyadenylation site can affect the coding sequence or, more often, 3′‐UTR length. In the latter case, stability, translational efficiency or localisation of the RNA may be affected. Histone mRNAs are an exception: Their precursors are cleaved by a partially different set of factors, and no poly(A) tail is added. Key Concepts The 3′‐ends of eukaryotic mRNAs are generated by processing of the primary transcript, not by transcription termination. 3′‐end processing is essential for the production of mRNAs. 3′‐end processing takes place in the cell nucleus and consists of cleavage of the primary transcript followed by addition of a poly(A) tail to the upstream cleavage product. The machinery for 3′‐end processing is complex, comprising at least 13 polypeptides. 3′‐end processing occurs cotranscriptionally and is coupled to transcription and splicing. Alternative polyadenylation, that is the choice of different sites for cleavage and polyadenylation, can change the protein sequence encoded by the resulting mRNAs and/or mRNA regulation. Histone mRNAs in metazoans are the only known RNAs that are not polyadenylated; their 3′‐ends are generated by a simple cleavage reaction.