Limits...
SERpredict: detection of tissue- or tumor-specific isoforms generated through exonization of transposable elements.

Mersch B, Sela N, Ast G, Suhai S, Hotz-Wagenblatt A - BMC Genet. (2007)

Bottom Line: Several examples in the literature show that isoforms generated by an exonization are specific to a certain tissue (for example the heart muscle) or inflict a disease.Thus, exonizations can have negative effects for the transcriptome of an organism.With this pipeline, we found several genes in which a transposed element formed a tissue- or tumor-specific isoform.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Biophysics, German Cancer Research Center (DKFZ), Heidelberg, Germany. b.mersch@dkfz.de

ABSTRACT

Background: Transposed elements (TEs) are known to affect transcriptomes, because either new exons are generated from intronic transposed elements (this is called exonization), or the element inserts into the exon, leading to a new transcript. Several examples in the literature show that isoforms generated by an exonization are specific to a certain tissue (for example the heart muscle) or inflict a disease. Thus, exonizations can have negative effects for the transcriptome of an organism.

Results: As we aimed at detecting other tissue- or tumor-specific isoforms in human and mouse genomes which were generated through exonization of a transposed element, we designed the automated analysis pipeline SERpredict (SER = Specific Exonized Retroelement) making use of Bayesian Statistics. With this pipeline, we found several genes in which a transposed element formed a tissue- or tumor-specific isoform.

Conclusion: Our results show that SERpredict produces relevant results, demonstrating the importance of transposed elements in shaping both the human and the mouse transcriptomes. The effect of transposed elements on the human transcriptome is several times higher than the effect on the mouse transcriptome, due to the contribution of the primate-specific Alu elements.

Show MeSH

Related in: MedlinePlus

The effects of TE insertions. a) (i) TE inserts into an intron of a gene. (ii-v) show the possible effects of this integration; (ii) alternatively exon is created, (iii) TE contributes alternative 5'splice site, (iv) TE contributes alternative 3'splice site, (v) TE creates a constitutively spliced exon. b) (i) TE inserts into the first or last exon of a gene. (ii – iv) show the possible effect of this integration: (ii, iii) enlargement of first or last exon, (iv) TE activates an alternative intron.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2194731&req=5

Figure 1: The effects of TE insertions. a) (i) TE inserts into an intron of a gene. (ii-v) show the possible effects of this integration; (ii) alternatively exon is created, (iii) TE contributes alternative 5'splice site, (iv) TE contributes alternative 3'splice site, (v) TE creates a constitutively spliced exon. b) (i) TE inserts into the first or last exon of a gene. (ii – iv) show the possible effect of this integration: (ii, iii) enlargement of first or last exon, (iv) TE activates an alternative intron.

Mentions: Mutations within intronic TEs may yield active splice sites which can be used instead of the normal splice sites, leading to the partial exonization of the intronic TE. However, the other TEs of the human and mouse genomes can be exonized, too. In a previous study, Sela et al. [7] showed that 1824 TEs are exonized in the human genome, of which about 58% are Alus. In the mouse genome, 506 transposed elements are exonized, most of which are either B1 or L1 elements (26% and 20%, respectively). Thus, transposed elements can affect the transcriptome. Either new exons are generated from intronic TEs (see Figure 1a (i)), or the TE inserts into the first or last exon of a gene (Figure 1b (i)), leading to a new transcript [8]. In the first case, the exonization can either generate an internal cassette exon (Figure 1a (ii)), an alternative 3'splice site (Figure 1a (iii)), an alternative 5'splice site (Figure 1a (iv)) or a constitutively spliced exon (Figure 1a (v)) [7,9]. In the case of insertions into first or last exons, the insertions cause either an elongation of the first/last exon (Figure 1b (ii, iii)) or an activation of an alternative intron (Figure 1b (iv)). For the exact number of occurrences of the different events please refer to [7].


SERpredict: detection of tissue- or tumor-specific isoforms generated through exonization of transposable elements.

Mersch B, Sela N, Ast G, Suhai S, Hotz-Wagenblatt A - BMC Genet. (2007)

The effects of TE insertions. a) (i) TE inserts into an intron of a gene. (ii-v) show the possible effects of this integration; (ii) alternatively exon is created, (iii) TE contributes alternative 5'splice site, (iv) TE contributes alternative 3'splice site, (v) TE creates a constitutively spliced exon. b) (i) TE inserts into the first or last exon of a gene. (ii – iv) show the possible effect of this integration: (ii, iii) enlargement of first or last exon, (iv) TE activates an alternative intron.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2194731&req=5

Figure 1: The effects of TE insertions. a) (i) TE inserts into an intron of a gene. (ii-v) show the possible effects of this integration; (ii) alternatively exon is created, (iii) TE contributes alternative 5'splice site, (iv) TE contributes alternative 3'splice site, (v) TE creates a constitutively spliced exon. b) (i) TE inserts into the first or last exon of a gene. (ii – iv) show the possible effect of this integration: (ii, iii) enlargement of first or last exon, (iv) TE activates an alternative intron.
Mentions: Mutations within intronic TEs may yield active splice sites which can be used instead of the normal splice sites, leading to the partial exonization of the intronic TE. However, the other TEs of the human and mouse genomes can be exonized, too. In a previous study, Sela et al. [7] showed that 1824 TEs are exonized in the human genome, of which about 58% are Alus. In the mouse genome, 506 transposed elements are exonized, most of which are either B1 or L1 elements (26% and 20%, respectively). Thus, transposed elements can affect the transcriptome. Either new exons are generated from intronic TEs (see Figure 1a (i)), or the TE inserts into the first or last exon of a gene (Figure 1b (i)), leading to a new transcript [8]. In the first case, the exonization can either generate an internal cassette exon (Figure 1a (ii)), an alternative 3'splice site (Figure 1a (iii)), an alternative 5'splice site (Figure 1a (iv)) or a constitutively spliced exon (Figure 1a (v)) [7,9]. In the case of insertions into first or last exons, the insertions cause either an elongation of the first/last exon (Figure 1b (ii, iii)) or an activation of an alternative intron (Figure 1b (iv)). For the exact number of occurrences of the different events please refer to [7].

Bottom Line: Several examples in the literature show that isoforms generated by an exonization are specific to a certain tissue (for example the heart muscle) or inflict a disease.Thus, exonizations can have negative effects for the transcriptome of an organism.With this pipeline, we found several genes in which a transposed element formed a tissue- or tumor-specific isoform.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Biophysics, German Cancer Research Center (DKFZ), Heidelberg, Germany. b.mersch@dkfz.de

ABSTRACT

Background: Transposed elements (TEs) are known to affect transcriptomes, because either new exons are generated from intronic transposed elements (this is called exonization), or the element inserts into the exon, leading to a new transcript. Several examples in the literature show that isoforms generated by an exonization are specific to a certain tissue (for example the heart muscle) or inflict a disease. Thus, exonizations can have negative effects for the transcriptome of an organism.

Results: As we aimed at detecting other tissue- or tumor-specific isoforms in human and mouse genomes which were generated through exonization of a transposed element, we designed the automated analysis pipeline SERpredict (SER = Specific Exonized Retroelement) making use of Bayesian Statistics. With this pipeline, we found several genes in which a transposed element formed a tissue- or tumor-specific isoform.

Conclusion: Our results show that SERpredict produces relevant results, demonstrating the importance of transposed elements in shaping both the human and the mouse transcriptomes. The effect of transposed elements on the human transcriptome is several times higher than the effect on the mouse transcriptome, due to the contribution of the primate-specific Alu elements.

Show MeSH
Related in: MedlinePlus