Limits...
Alternative splicing and co-option of transposable elements: the case of TMPO/LAP2α and ZNF451 in mammals.

Abascal F, Tress ML, Valencia A - Bioinformatics (2015)

Bottom Line: We found that these LAP2alpha domains have sequence similarity to repetitive sequences in non-mammalian genomes, which are in turn related to the first ORF from a DIRS1-like retrotransposon.This retrotransposon domestication happened separately and resulted in proteins that combine retrotransposon and host protein domains.The LAP2alpha-specific isoform of TMPO (LAP2α) has been co-opted for important roles in the cell, whereas the ZNF451 LAP2alpha isoform is evolving under strong purifying selection but remains uncharacterized.

View Article: PubMed Central - PubMed

Affiliation: Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre, Madrid 28029, Spain.

No MeSH data available.


Schematic organization of the ZNF451 and TMPO transcripts (A) and the domain organization of the translated protein isoforms (B). The presence of a LAP2alpha domain within ZNF451-L2a is supported by an Hmmscan search against Pfam (e value of 1.5e-08). The LAP2alpha domain of both TMPO and ZNF451 is coded by a large 3-prime exon. The exon includes a polyadenylation signal that prevents the simultaneous incorporation of other exons. In the case of ZNF451, alternatively skipped 3-prime exons code for multiple Zinc fingers. In the case of TMPO, they code for the C-terminal half of the protein, which includes a nuclear membrane attachment trans-membrane helix. The exon coding the LAP2alpha domain translates into amino acid regions of 497 and 506 residues (9114 and 2812 bp) in ZNF451 and TMPO, respectively
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4495291&req=5

btv132-F1: Schematic organization of the ZNF451 and TMPO transcripts (A) and the domain organization of the translated protein isoforms (B). The presence of a LAP2alpha domain within ZNF451-L2a is supported by an Hmmscan search against Pfam (e value of 1.5e-08). The LAP2alpha domain of both TMPO and ZNF451 is coded by a large 3-prime exon. The exon includes a polyadenylation signal that prevents the simultaneous incorporation of other exons. In the case of ZNF451, alternatively skipped 3-prime exons code for multiple Zinc fingers. In the case of TMPO, they code for the C-terminal half of the protein, which includes a nuclear membrane attachment trans-membrane helix. The exon coding the LAP2alpha domain translates into amino acid regions of 497 and 506 residues (9114 and 2812 bp) in ZNF451 and TMPO, respectively

Mentions: Very few human protein-coding genes generate alternative isoforms in which one Pfam functional domain (Finn et al., 2014) is substituted for another. ZNF451 is one of just nine of these genes. One of the two ZNF451 splice isoforms has a single large 3′-exon with a polyadenylation signal that codes for a C-terminal ‘LAP2alpha’ domain. The incorporation of the polyadenylation signal prevents the incorporation of downstream exons coding for multiple zinc fingers (Fig. 1). The LAP2alpha domain is found in just one other human gene, TMPO. TMPO has a similar pattern of alternative splicing to ZNF451, here the LAP2alpha C-terminal domain replaces a protein region that contains a nuclear attachment trans-membrane (TM) region (Fig. 1). The TMPO LAP2alpha isoform is known as LAP2α, whereas the ZNF451 isoform is referred to as ZNF451-L2a in this work.Fig. 1.


Alternative splicing and co-option of transposable elements: the case of TMPO/LAP2α and ZNF451 in mammals.

Abascal F, Tress ML, Valencia A - Bioinformatics (2015)

Schematic organization of the ZNF451 and TMPO transcripts (A) and the domain organization of the translated protein isoforms (B). The presence of a LAP2alpha domain within ZNF451-L2a is supported by an Hmmscan search against Pfam (e value of 1.5e-08). The LAP2alpha domain of both TMPO and ZNF451 is coded by a large 3-prime exon. The exon includes a polyadenylation signal that prevents the simultaneous incorporation of other exons. In the case of ZNF451, alternatively skipped 3-prime exons code for multiple Zinc fingers. In the case of TMPO, they code for the C-terminal half of the protein, which includes a nuclear membrane attachment trans-membrane helix. The exon coding the LAP2alpha domain translates into amino acid regions of 497 and 506 residues (9114 and 2812 bp) in ZNF451 and TMPO, respectively
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4495291&req=5

btv132-F1: Schematic organization of the ZNF451 and TMPO transcripts (A) and the domain organization of the translated protein isoforms (B). The presence of a LAP2alpha domain within ZNF451-L2a is supported by an Hmmscan search against Pfam (e value of 1.5e-08). The LAP2alpha domain of both TMPO and ZNF451 is coded by a large 3-prime exon. The exon includes a polyadenylation signal that prevents the simultaneous incorporation of other exons. In the case of ZNF451, alternatively skipped 3-prime exons code for multiple Zinc fingers. In the case of TMPO, they code for the C-terminal half of the protein, which includes a nuclear membrane attachment trans-membrane helix. The exon coding the LAP2alpha domain translates into amino acid regions of 497 and 506 residues (9114 and 2812 bp) in ZNF451 and TMPO, respectively
Mentions: Very few human protein-coding genes generate alternative isoforms in which one Pfam functional domain (Finn et al., 2014) is substituted for another. ZNF451 is one of just nine of these genes. One of the two ZNF451 splice isoforms has a single large 3′-exon with a polyadenylation signal that codes for a C-terminal ‘LAP2alpha’ domain. The incorporation of the polyadenylation signal prevents the incorporation of downstream exons coding for multiple zinc fingers (Fig. 1). The LAP2alpha domain is found in just one other human gene, TMPO. TMPO has a similar pattern of alternative splicing to ZNF451, here the LAP2alpha C-terminal domain replaces a protein region that contains a nuclear attachment trans-membrane (TM) region (Fig. 1). The TMPO LAP2alpha isoform is known as LAP2α, whereas the ZNF451 isoform is referred to as ZNF451-L2a in this work.Fig. 1.

Bottom Line: We found that these LAP2alpha domains have sequence similarity to repetitive sequences in non-mammalian genomes, which are in turn related to the first ORF from a DIRS1-like retrotransposon.This retrotransposon domestication happened separately and resulted in proteins that combine retrotransposon and host protein domains.The LAP2alpha-specific isoform of TMPO (LAP2α) has been co-opted for important roles in the cell, whereas the ZNF451 LAP2alpha isoform is evolving under strong purifying selection but remains uncharacterized.

View Article: PubMed Central - PubMed

Affiliation: Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre, Madrid 28029, Spain.

No MeSH data available.