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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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Poly(A) sites and L2 and MIR. (A) Distribution of poly(A) sites in the 3′-end region of L2a subfamily of L2. (B) Alignment of the 3′-end region of L2a with MIRb. AATAAA, ATTAAA, TGTA are shown in green. Identical nucleotides are indicated by asterisks. (C) Distribution of poly(A) sites in MIRb subfamily of MIR. See the legend of Figure 4B for description of (A) and (C).
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Figure 5: Poly(A) sites and L2 and MIR. (A) Distribution of poly(A) sites in the 3′-end region of L2a subfamily of L2. (B) Alignment of the 3′-end region of L2a with MIRb. AATAAA, ATTAAA, TGTA are shown in green. Identical nucleotides are indicated by asterisks. (C) Distribution of poly(A) sites in MIRb subfamily of MIR. See the legend of Figure 4B for description of (A) and (C).

Mentions: L2 is the second top LINE associated with poly(A) sites. Most associated poly(A) sites are located within or near its 3′-end region, as shown for L2a, the top subfamily of L2 (Figure 5A). Interestingly, the last 50 nt region of its plus strand tends to be located upstream of poly(A) site, whereas the minus strand of this region tends to be located downstream of poly(A) site (Figure 5A). Consistent with this observation, this region contains an AATAAA PAS and a TGTA element on the plus strand and a TGTG element on the minus strand (Figure 5B). Since the 3′-end region of L2 is highly homologous to the 3′-end region of Mammalian-wide interspersed repeat (MIR), a tRNA-derived SINE that is thought to be active ∼130 MYR ago, in the same period as L2 (53,54), it is not surprising to see that MIR has a similar trend for poly(A) site association (Figure 5C). For example, MIRb, the top MIR subfamily, contains both ATTAAA and AATAAA PAS and a TGTA element on the plus strand and two TGTG elements on the minus strand (Figure 5B). Thus, MIR and L2 can bring either upstream or downstream cis-elements for polyadenylation to the genome, and give rise to new poly(A) sites. Notably, consistent with their evolutionary history, MIR and L2 together account for about half of the conserved TE-associated poly(A) sites, indicating their significant contribution to poly(A) site evolution in mammals.Figure 5.


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)

Poly(A) sites and L2 and MIR. (A) Distribution of poly(A) sites in the 3′-end region of L2a subfamily of L2. (B) Alignment of the 3′-end region of L2a with MIRb. AATAAA, ATTAAA, TGTA are shown in green. Identical nucleotides are indicated by asterisks. (C) Distribution of poly(A) sites in MIRb subfamily of MIR. See the legend of Figure 4B for description of (A) and (C).
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Figure 5: Poly(A) sites and L2 and MIR. (A) Distribution of poly(A) sites in the 3′-end region of L2a subfamily of L2. (B) Alignment of the 3′-end region of L2a with MIRb. AATAAA, ATTAAA, TGTA are shown in green. Identical nucleotides are indicated by asterisks. (C) Distribution of poly(A) sites in MIRb subfamily of MIR. See the legend of Figure 4B for description of (A) and (C).
Mentions: L2 is the second top LINE associated with poly(A) sites. Most associated poly(A) sites are located within or near its 3′-end region, as shown for L2a, the top subfamily of L2 (Figure 5A). Interestingly, the last 50 nt region of its plus strand tends to be located upstream of poly(A) site, whereas the minus strand of this region tends to be located downstream of poly(A) site (Figure 5A). Consistent with this observation, this region contains an AATAAA PAS and a TGTA element on the plus strand and a TGTG element on the minus strand (Figure 5B). Since the 3′-end region of L2 is highly homologous to the 3′-end region of Mammalian-wide interspersed repeat (MIR), a tRNA-derived SINE that is thought to be active ∼130 MYR ago, in the same period as L2 (53,54), it is not surprising to see that MIR has a similar trend for poly(A) site association (Figure 5C). For example, MIRb, the top MIR subfamily, contains both ATTAAA and AATAAA PAS and a TGTA element on the plus strand and two TGTG elements on the minus strand (Figure 5B). Thus, MIR and L2 can bring either upstream or downstream cis-elements for polyadenylation to the genome, and give rise to new poly(A) sites. Notably, consistent with their evolutionary history, MIR and L2 together account for about half of the conserved TE-associated poly(A) sites, indicating their significant contribution to poly(A) site evolution in mammals.Figure 5.

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