Signals for pre-mRNA cleavage and polyadenylation

Abstract

Pre-mRNA cleavage and polyadenylation is an essential step for 3' end formation of almost all protein-coding transcripts in eukaryotes. The reaction, involving cleavage of nascent mRNA followed by addition of a polyadenylate or poly(A) tail, is controlled by cis-acting elements in the pre-mRNA surrounding the cleavage site. Experimental and bioinformatic studies in the past three decades have elucidated conserved and divergent elements across eukaryotes, from yeast to human. Here we review histories and current models of these elements in a broad range of species.

FIGURE 1

Alternative polyA sites in a gene. PolyA sites can be located in different parts of a gene, as indicated in the graph. Boxes are exons. pA, polyA site; AAA, poly(A) tail; ORF, open reading frame.

FIGURE 2

PolyA signals in different species. (a) Metazoans: elements that are restricted to certain species are indicated. M, mammal; B, bird; F, fish; A, arthropod; N, nematode; pA, polyA site. (b) Yeast. (c) Plants, including land plants and freshwater algae (Streptophyta), most green algae (Chlorophyta), and the special case of Chlamydomonas reinhardtii.

FIGURE 3

PolyA sites in Caenorhabditis elegans. (a) Three types of polyA sites. Terminal sites occur on monocistronic genes, or on 3′ terminal genes in polycistronic operons. Internal sites occur on non-terminal genes in operons. SL-1 type sites are a special class of internal sites characterized by exact overlap of the upstream polyA site and the downstream trans-splicing site. (b) Adjacent polyA sites of the same gene sharing cis elements. Arrowed lines represent pre-mRNAs containing cis elements (shown as boxes) and polyA sites (shown as vertical arrows). Cis elements used by both polyA sites are indicated by shaded boxes. (c) Adjacent polyA sites of genes on opposite strands. As in (b), arrowed lines represent pre-mRNAs with arrows indicating direction of transcription. Shaded boxes indicate that both sense and antisense sequences are polyA signals. pA, polyA site.

FIGURE 4

Mammalian and yeast polyA factors and complexes and their interactions with polyA signals. Protein–RNA interactions are indicated by arrows. Homologous proteins are listed in the same row. Both mammalian and yeast complexes and subcomplexes are indicated. CS, cleavage site; poly(A), poly(A) tail.