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Conservation of CD44 exon v3 functional elements in mammals.

Vela E, Hilari JM, Delclaux M, Fernández-Bellon H, Isamat M - BMC Res Notes (2008)

Bottom Line: We also report the functional expression of CD44v3 isoforms in peripheral blood cells of different mammalian taxa with both consensus and variant v3 sequences.CD44v3 mammalian sequences maintain all functional splicing regulatory elements as well as the GAG binding site with the same relative positions and sequence identity previously described during alternative splicing of human CD44.Amplification of CD44v3 sequence from mammalian species but not from birds, fish or reptiles, may lead to classify CD44v3 as an exclusive mammalian gene trait.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of R+D+1, Laboratorio Dr. Echevanne, Barcelona, Spain. evela@echevame.com

ABSTRACT

Background: The human CD44 gene contains 10 variable exons (v1 to v10) that can be alternatively spliced to generate hundreds of different CD44 protein isoforms. Human CD44 variable exon v3 inclusion in the final mRNA depends on a multisite bipartite splicing enhancer located within the exon itself, which we have recently described, and provides the protein domain responsible for growth factor binding to CD44.

Findings: We have analyzed the sequence of CD44v3 in 95 mammalian species to report high conservation levels for both its splicing regulatory elements (the 3' splice site and the exonic splicing enhancer), and the functional glycosaminglycan binding site coded by v3. We also report the functional expression of CD44v3 isoforms in peripheral blood cells of different mammalian taxa with both consensus and variant v3 sequences.

Conclusion: CD44v3 mammalian sequences maintain all functional splicing regulatory elements as well as the GAG binding site with the same relative positions and sequence identity previously described during alternative splicing of human CD44. The sequence within the GAG attachment site, which in turn contains the Y motif of the exonic splicing enhancer, is more conserved relative to the rest of exon. Amplification of CD44v3 sequence from mammalian species but not from birds, fish or reptiles, may lead to classify CD44v3 as an exclusive mammalian gene trait.

No MeSH data available.


CD44 exon v3. A) Genomic structure of human CD44 gene (gray boxes, constitutive exons; white boxes, alternative exons; black box, variable exon v3; black line, introns). B) Schematic representation of exon v3 and its flanking introns (gray boxes, relative location of the XX and Y splicing enhancer motifs; white box, relative location of the nucleotides coding for the GAG binding site and the SGSG motif). Genomic DNA amplification was performed with PCR primers located in intron 6 and in the v3-intron 7 junction (indicated by arrows).
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Figure 1: CD44 exon v3. A) Genomic structure of human CD44 gene (gray boxes, constitutive exons; white boxes, alternative exons; black box, variable exon v3; black line, introns). B) Schematic representation of exon v3 and its flanking introns (gray boxes, relative location of the XX and Y splicing enhancer motifs; white box, relative location of the nucleotides coding for the GAG binding site and the SGSG motif). Genomic DNA amplification was performed with PCR primers located in intron 6 and in the v3-intron 7 junction (indicated by arrows).

Mentions: The CD44 family of transmembrane glycoproteins mediates the response of cells to their extracellular microenvironment by regulating growth, survival, differentiation and motility. All human CD44 proteins are encoded by a single, highly conserved gene containing 20 exons, 12 of each undergo alternative splicing [1] (see figure 1A). Complex alternative splicing of the central region of the gene is responsible for the incorporation of the variable domains to shape, predominantly, the extracellular, membrane-proximal stem structure of the protein. The heterogeneity of the CD44 protein products can be further increased by post-translational modifications [1-4]. The sequence encoded in exon v3 contains an optimal Ser-Gly-Ser-Gly (SGSG) consensus motif for modification by heparan sulfate (HS) side chains, to which several heparin-binding proteins attach [5]. This unique HS addition site is critical for CD44v3 isoforms' capacity to bind and present HS-dependent growth factors.


Conservation of CD44 exon v3 functional elements in mammals.

Vela E, Hilari JM, Delclaux M, Fernández-Bellon H, Isamat M - BMC Res Notes (2008)

CD44 exon v3. A) Genomic structure of human CD44 gene (gray boxes, constitutive exons; white boxes, alternative exons; black box, variable exon v3; black line, introns). B) Schematic representation of exon v3 and its flanking introns (gray boxes, relative location of the XX and Y splicing enhancer motifs; white box, relative location of the nucleotides coding for the GAG binding site and the SGSG motif). Genomic DNA amplification was performed with PCR primers located in intron 6 and in the v3-intron 7 junction (indicated by arrows).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2531186&req=5

Figure 1: CD44 exon v3. A) Genomic structure of human CD44 gene (gray boxes, constitutive exons; white boxes, alternative exons; black box, variable exon v3; black line, introns). B) Schematic representation of exon v3 and its flanking introns (gray boxes, relative location of the XX and Y splicing enhancer motifs; white box, relative location of the nucleotides coding for the GAG binding site and the SGSG motif). Genomic DNA amplification was performed with PCR primers located in intron 6 and in the v3-intron 7 junction (indicated by arrows).
Mentions: The CD44 family of transmembrane glycoproteins mediates the response of cells to their extracellular microenvironment by regulating growth, survival, differentiation and motility. All human CD44 proteins are encoded by a single, highly conserved gene containing 20 exons, 12 of each undergo alternative splicing [1] (see figure 1A). Complex alternative splicing of the central region of the gene is responsible for the incorporation of the variable domains to shape, predominantly, the extracellular, membrane-proximal stem structure of the protein. The heterogeneity of the CD44 protein products can be further increased by post-translational modifications [1-4]. The sequence encoded in exon v3 contains an optimal Ser-Gly-Ser-Gly (SGSG) consensus motif for modification by heparan sulfate (HS) side chains, to which several heparin-binding proteins attach [5]. This unique HS addition site is critical for CD44v3 isoforms' capacity to bind and present HS-dependent growth factors.

Bottom Line: We also report the functional expression of CD44v3 isoforms in peripheral blood cells of different mammalian taxa with both consensus and variant v3 sequences.CD44v3 mammalian sequences maintain all functional splicing regulatory elements as well as the GAG binding site with the same relative positions and sequence identity previously described during alternative splicing of human CD44.Amplification of CD44v3 sequence from mammalian species but not from birds, fish or reptiles, may lead to classify CD44v3 as an exclusive mammalian gene trait.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of R+D+1, Laboratorio Dr. Echevanne, Barcelona, Spain. evela@echevame.com

ABSTRACT

Background: The human CD44 gene contains 10 variable exons (v1 to v10) that can be alternatively spliced to generate hundreds of different CD44 protein isoforms. Human CD44 variable exon v3 inclusion in the final mRNA depends on a multisite bipartite splicing enhancer located within the exon itself, which we have recently described, and provides the protein domain responsible for growth factor binding to CD44.

Findings: We have analyzed the sequence of CD44v3 in 95 mammalian species to report high conservation levels for both its splicing regulatory elements (the 3' splice site and the exonic splicing enhancer), and the functional glycosaminglycan binding site coded by v3. We also report the functional expression of CD44v3 isoforms in peripheral blood cells of different mammalian taxa with both consensus and variant v3 sequences.

Conclusion: CD44v3 mammalian sequences maintain all functional splicing regulatory elements as well as the GAG binding site with the same relative positions and sequence identity previously described during alternative splicing of human CD44. The sequence within the GAG attachment site, which in turn contains the Y motif of the exonic splicing enhancer, is more conserved relative to the rest of exon. Amplification of CD44v3 sequence from mammalian species but not from birds, fish or reptiles, may lead to classify CD44v3 as an exclusive mammalian gene trait.

No MeSH data available.