Alternative Polyadenylation in the Human Genome: Evolution


Messenger ribonucleic acid (mRNA) polyadenylation is an essential step for the maturation of most eukaryotic mRNAs, and is tightly coupled with termination of transcription. Over half of all human genes have alternative polyadenylation sites, resulting in transcript variants with different 3′ UTR (untranslated region) sequences and, in some cases, protein‐coding regions. Comparative genomic studies are beginning to elucidate the phylogenetics of cis‐elements and protein factors involved in the regulation of mRNA polyadenylation, and shed light on the evolution of alternative polyadenylation.

Keywords: mRNA polyadenylation; evolution; cis‐elements; splicing; 3′ UTR

Figure 1.

Cis‐elements in mRNA polyadenylation. A poly(A) site region is shown, with a poly(A) site (pA) in the middle. Cis‐elements that have been phylogenetically analysed are listed in a table containing different species and evolutionary groups. ‘+’ and ‘−’ indicate presence or absence of polyadenylation of cis‐elements in a species. ‘?’ indicates that the cis‐element has not been biochemically examined.

Figure 2.

Types of alternative polyadenylation. Alternative polyadenylation in the 3′‐most exon result in alternative 3′ UTRs. Alternative polyadenylation in introns can result in two forms of alternative terminal exons, i.e. composite terminal exon and skipped terminal exon. ORF, open reading frame.

Figure 3.

Alternative polyadenylation in 3′‐most exons. (a) Usage of human alternative polyadenylation sites. (b) Human 3′ UTR lengths resulting from alternative polyadenylation. Median 3′ UTR lengths are shown above the graph. The 5′‐ and 3′‐most poly(A) sites are those located 5′‐ and 3′‐most sites in 3′‐most exons. The middle poly(A) sites are located between 5′‐ and 3′‐most poly(A) sites. Poly(A) sites conserved in mouse are shown as ‘C’ and nonconserved one as ‘N’.

Figure 4.

Transposable elements (TEs) and alternative poly(A) sites. Poly(A) sites conserved in mouse are shown as ‘C’ and nonconserved one as ‘N’.

Figure 5.

Interplay between splicing and polyadenylation. ‘+’ indicates activation and ‘−’ indicates inhibition. pA, poly(A) site; the ‘A’ between 5′ss and 3′ss represents the branch point of intron.



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Further Reading

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Tian, Bin(Jul 2008) Alternative Polyadenylation in the Human Genome: Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020768]