Abstract
BackgroundAlternative polyadenylation is a widespread mechanism contributing to transcript diversity in eukaryotes. Over half of mammalian genes are alternatively polyadenylated. Our understanding of poly(A) site evolution is limited by the lack of a reliable identification of conserved, equivalent poly(A) sites among species. We introduce here a working definition of conserved poly(A) sites as sites that are both (i) properly aligned in human and mouse orthologous 3' untranslated regions (UTRs) and (ii) supported by EST or cDNA data in both species.ResultsWe identified about 4800 such conserved poly(A) sites covering one third of the orthologous gene set studied. Characteristics of conserved poly(A) sites such as processing efficiency and tissue-specificity were analyzed. Conserved sites show a higher processing efficiency but no difference in tissular distribution when compared to non-conserved sites. In general, alternative poly(A) sites are species-specific and involve minor, non-conserved sites that are unlikely to play essential roles. However, there are about 500 genes with conserved tandem poly(A) sites. A significant fraction of these conserved tandems display a conserved arrangement of major/minor sites in their 3' UTR, suggesting that these alternative 3' ends may be under selection.ConclusionThis analysis allows us to identify potential functional alternative poly(A) sites and provides clues on the selective mechanisms at play in the appearance of multiple poly(A) sites and their maintenance in the 3' UTRs of genes.
Highlights
Alternative polyadenylation is a widespread mechanism contributing to transcript diversity in eukaryotes
We introduce here a method to perform this assignment using both multiple alignments of 3'untranslated regions (UTRs) regions and EST mapping of polyadenylation sites
After clustering EST and cDNA hits, potential poly(A) sites were identified based on several quality criteria including the presence of at least two ESTs/cDNA ending at site, reduced dangling ends in Blast matches, lack of potential internal priming tract in downstream genomic region and presence of a canonical or variant poly(A) signal near 3' end
Summary
Alternative polyadenylation is a widespread mechanism contributing to transcript diversity in eukaryotes. We introduce here a working definition of conserved poly(A) sites as sites that are both (i) properly aligned in human and mouse orthologous 3' untranslated regions (UTRs) and (ii) supported by EST or cDNA data in both species. Alternative polyadenylation site selection is an important source of transcript diversity in higher eukaryotes. For at least 50% of genes in mammalian genomes, several polyadenylation sites are present and mRNAs with different 3'UTR regions can be produced from a single gene [24]. Alternative poly(A) sites are commonly classified into tandem poly(A) sites that locate in the same 3'-exon, and (page number not for citation purposes). The actual functional impact of tandem poly(A) sites, producing 3' ends that differ solely by the length of the 3' UTR, is still largely unknown
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