Computational analysis of 3'-ends of ESTs shows four classes of alternative polyadenylation in human, mouse, and rat

Abstract

Alternative initiation, splicing, and polyadenylation are key mechanisms used by many organisms to generate diversity among mature mRNA transcripts originating from the same transcription unit. While previous computational analyses of alternative polyadenylation have focused on polyadenylation activities within or downstream of the normal 3'-terminal exons, we present the results of the first genome-wide analysis of patterns of alternative polyadenylation in the human, mouse, and rat genomes occurring over the entire transcribed regions of mRNAs using 3'-ESTs with poly(A) tails aligned to genomic sequences. Four distinct classes of patterns of alternative polyadenylation result from this analysis: tandem poly(A) sites, composite exons, hidden exons, and truncated exons. We estimate that at least 49% (human), 31% (mouse), and 28% (rat) of polyadenylated transcription units have alternative polyadenylation. A portion of these alternative polyadenylation events result in new protein isoforms.

Figure 1.

Four classes of patterns of alternative polyadenylation are shown together with the reference sequence. (A) Tandem poly(A) sites. (B) Composite exons. (C) Hidden exons. (D) Truncated exons.

Figure 2.

Comparison between the full-length mRNA alignments and the poly(A) EST alignments of Lamin A/C in (A) human, (B) mouse, and (C) rat. In all three species, poly(A) ESTs are clustered into two clusters, each corresponding to a poly(A) site. Lamin A and C isoforms are present in all three species. In human, a third isoform, Lamin Adel10, skips exon 10 of Lamin A. In mouse and rat, a third isoform, Lamin C2, has alternative initiation. GenBank gi numbers are shown for all mRNAs and ESTs.

Figure 2.

Comparison between the full-length mRNA alignments and the poly(A) EST alignments of Lamin A/C in (A) human, (B) mouse, and (C) rat. In all three species, poly(A) ESTs are clustered into two clusters, each corresponding to a poly(A) site. Lamin A and C isoforms are present in all three species. In human, a third isoform, Lamin Adel10, skips exon 10 of Lamin A. In mouse and rat, a third isoform, Lamin C2, has alternative initiation. GenBank gi numbers are shown for all mRNAs and ESTs.