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Phylogenetic analysis of mRNA polyadenylation sites reveals a role of transposable elements in evolution of the 3'-end of genes.

Lee JY, Ji Z, Tian B - Nucleic Acids Res. (2008)

Bottom Line: We found that the 3'-most poly(A) sites tend to be more conserved than upstream ones, whereas poly(A) sites located upstream of the 3'-most exon, also termed intronic poly(A) sites, tend to be much less conserved.We also found that nonconserved poly(A) sites are associated with transposable elements (TEs) to a much greater extent than conserved ones, albeit less frequently utilized.Our results establish a conservation pattern for alternative poly(A) sites in several vertebrate species, and indicate that the 3'-end of genes can be dynamically modified by TEs through evolution.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Biomedical Sciences and Department of Biochemistry and Molecular Biology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.

ABSTRACT
mRNA polyadenylation is an essential step for the maturation of almost all eukaryotic mRNAs, and is tightly coupled with termination of transcription in defining the 3'-end of genes. Large numbers of human and mouse genes harbor alternative polyadenylation sites [poly(A) sites] that lead to mRNA variants containing different 3'-untranslated regions (UTRs) and/or encoding distinct protein sequences. Here, we examined the conservation and divergence of different types of alternative poly(A) sites across human, mouse, rat and chicken. We found that the 3'-most poly(A) sites tend to be more conserved than upstream ones, whereas poly(A) sites located upstream of the 3'-most exon, also termed intronic poly(A) sites, tend to be much less conserved. Genes with longer evolutionary history are more likely to have alternative polyadenylation, suggesting gain of poly(A) sites through evolution. We also found that nonconserved poly(A) sites are associated with transposable elements (TEs) to a much greater extent than conserved ones, albeit less frequently utilized. Different classes of TEs have different characteristics in their association with poly(A) sites via exaptation of TE sequences into polyadenylation elements. Our results establish a conservation pattern for alternative poly(A) sites in several vertebrate species, and indicate that the 3'-end of genes can be dynamically modified by TEs through evolution.

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Schematic of alternative polyadenylation and different types of poly(A) site. Poly(A) sites are classified and named according to their location in a gene. The one letter code for each type is shown in parenthesis. (A) Single poly(A) sites (S). (B) Sites located in the 3′-most exon are classified into 5′-most site (F), middle site (M) and 3′-most site (L). (C) Sites located upstream of the 3′-most exon are considered intronic, and named composite terminal exon site (C), and skipped or hidden terminal exon sites (H), based on the gene splicing pattern. pA, poly(A) site; 5′ ss, 5′ splice site; AAA, poly(A) tail.
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Figure 1: Schematic of alternative polyadenylation and different types of poly(A) site. Poly(A) sites are classified and named according to their location in a gene. The one letter code for each type is shown in parenthesis. (A) Single poly(A) sites (S). (B) Sites located in the 3′-most exon are classified into 5′-most site (F), middle site (M) and 3′-most site (L). (C) Sites located upstream of the 3′-most exon are considered intronic, and named composite terminal exon site (C), and skipped or hidden terminal exon sites (H), based on the gene splicing pattern. pA, poly(A) site; 5′ ss, 5′ splice site; AAA, poly(A) tail.

Mentions: Over half of all human genes have multiple poly(A) sites (13,18), leading to alternative gene products and contributing to the complexity of the mRNA pool in human cells. Multiple poly(A) sites can be located downstream of the stop codon in the 3′-most exon (Figure 1), leading to transcripts with variable 3′-untranslated regions (UTRs), or in internal exons, leading to transcripts with variable protein products and 3′-UTRs. The latter case is also referred to as intronic polyadenylation, as poly(A) site usage is competed against by splicing (19). The selection of alternative poly(A) sites has been shown to be related to biological factors, such as development stage and cell condition, for a number of genes (20–24). Both the level of polyadenylation factors and tissue-specific usage of cis-elements have been implicated in alternative polyadenylation in different tissues (21,25,26).Figure 1.


Phylogenetic analysis of mRNA polyadenylation sites reveals a role of transposable elements in evolution of the 3'-end of genes.

Lee JY, Ji Z, Tian B - Nucleic Acids Res. (2008)

Schematic of alternative polyadenylation and different types of poly(A) site. Poly(A) sites are classified and named according to their location in a gene. The one letter code for each type is shown in parenthesis. (A) Single poly(A) sites (S). (B) Sites located in the 3′-most exon are classified into 5′-most site (F), middle site (M) and 3′-most site (L). (C) Sites located upstream of the 3′-most exon are considered intronic, and named composite terminal exon site (C), and skipped or hidden terminal exon sites (H), based on the gene splicing pattern. pA, poly(A) site; 5′ ss, 5′ splice site; AAA, poly(A) tail.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC2553571&req=5

Figure 1: Schematic of alternative polyadenylation and different types of poly(A) site. Poly(A) sites are classified and named according to their location in a gene. The one letter code for each type is shown in parenthesis. (A) Single poly(A) sites (S). (B) Sites located in the 3′-most exon are classified into 5′-most site (F), middle site (M) and 3′-most site (L). (C) Sites located upstream of the 3′-most exon are considered intronic, and named composite terminal exon site (C), and skipped or hidden terminal exon sites (H), based on the gene splicing pattern. pA, poly(A) site; 5′ ss, 5′ splice site; AAA, poly(A) tail.
Mentions: Over half of all human genes have multiple poly(A) sites (13,18), leading to alternative gene products and contributing to the complexity of the mRNA pool in human cells. Multiple poly(A) sites can be located downstream of the stop codon in the 3′-most exon (Figure 1), leading to transcripts with variable 3′-untranslated regions (UTRs), or in internal exons, leading to transcripts with variable protein products and 3′-UTRs. The latter case is also referred to as intronic polyadenylation, as poly(A) site usage is competed against by splicing (19). The selection of alternative poly(A) sites has been shown to be related to biological factors, such as development stage and cell condition, for a number of genes (20–24). Both the level of polyadenylation factors and tissue-specific usage of cis-elements have been implicated in alternative polyadenylation in different tissues (21,25,26).Figure 1.

Bottom Line: We found that the 3'-most poly(A) sites tend to be more conserved than upstream ones, whereas poly(A) sites located upstream of the 3'-most exon, also termed intronic poly(A) sites, tend to be much less conserved.We also found that nonconserved poly(A) sites are associated with transposable elements (TEs) to a much greater extent than conserved ones, albeit less frequently utilized.Our results establish a conservation pattern for alternative poly(A) sites in several vertebrate species, and indicate that the 3'-end of genes can be dynamically modified by TEs through evolution.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Biomedical Sciences and Department of Biochemistry and Molecular Biology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.

ABSTRACT
mRNA polyadenylation is an essential step for the maturation of almost all eukaryotic mRNAs, and is tightly coupled with termination of transcription in defining the 3'-end of genes. Large numbers of human and mouse genes harbor alternative polyadenylation sites [poly(A) sites] that lead to mRNA variants containing different 3'-untranslated regions (UTRs) and/or encoding distinct protein sequences. Here, we examined the conservation and divergence of different types of alternative poly(A) sites across human, mouse, rat and chicken. We found that the 3'-most poly(A) sites tend to be more conserved than upstream ones, whereas poly(A) sites located upstream of the 3'-most exon, also termed intronic poly(A) sites, tend to be much less conserved. Genes with longer evolutionary history are more likely to have alternative polyadenylation, suggesting gain of poly(A) sites through evolution. We also found that nonconserved poly(A) sites are associated with transposable elements (TEs) to a much greater extent than conserved ones, albeit less frequently utilized. Different classes of TEs have different characteristics in their association with poly(A) sites via exaptation of TE sequences into polyadenylation elements. Our results establish a conservation pattern for alternative poly(A) sites in several vertebrate species, and indicate that the 3'-end of genes can be dynamically modified by TEs through evolution.

Show MeSH