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Alternative splicing of human NT5E in cirrhosis and hepatocellular carcinoma produces a negative regulator of ecto-5'-nucleotidase (CD73).

Snider NT, Altshuler PJ, Wan S, Welling TH, Cavalcoli J, Omary MB - Mol. Biol. Cell (2014)

Bottom Line: The two human isoforms exhibited functional differences, such that ectopic expression of canonical CD73 (CD73L) in human HepG2 cells was associated with decreased expression of the proliferation marker Ki67, whereas CD73S expression did not have an effect on Ki67 expression.Furthermore, CD73S complexed with CD73L and promoted proteasome-dependent CD73L degradation.The findings reveal species-specific CD73 regulation, with potential significance to cancer, fibrosis, and other diseases characterized by changes in CD73 expression and function.

View Article: PubMed Central - PubMed

Affiliation: Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109.

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The human NT5E gene is regulated by alternative splicing. (A) Species comparison of the number of NT5E predicted transcripts using the Ensembl database. (B) Human NT5E has five splice variants, all predicted to be protein coding (bp, base pairs; aa, amino acids), but only two are annotated by CCDS. (C) The CCDS-validated transcripts NT5E-001 (NT5E-1) and NT5E-201 (NT5E-2), which differ with respect to the presence of exon 7 (arrow) in NT5E-1, are shown schematically.
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Figure 1: The human NT5E gene is regulated by alternative splicing. (A) Species comparison of the number of NT5E predicted transcripts using the Ensembl database. (B) Human NT5E has five splice variants, all predicted to be protein coding (bp, base pairs; aa, amino acids), but only two are annotated by CCDS. (C) The CCDS-validated transcripts NT5E-001 (NT5E-1) and NT5E-201 (NT5E-2), which differ with respect to the presence of exon 7 (arrow) in NT5E-1, are shown schematically.

Mentions: Using the Ensembl genome browser (Flicek et al., 2014), we compared the alternative splicing pattern of human NT5E to nine other vertebrate species. Whereas human NT5E encodes five transcripts, all other species, except for cow, are predicted to have one NT5E transcript (Figure 1A). Aside from NT5E-001, which encodes the full-length canonical CD73 protein, NT5E-201 (Figure 1B) is the only other human transcript annotated by the Collaborative Consensus Coding Sequence (CCDS) project (Harte et al., 2012) as being highly likely to encode a protein. Therefore we focused our subsequent analysis on comparing these two transcripts, and we refer to NT5E-001 and NT5E-201 as NT5E-1 and NT5E-2, respectively. The only difference between the two transcripts is the absence of exon 7 in NT5E-2 (Figure 1C).


Alternative splicing of human NT5E in cirrhosis and hepatocellular carcinoma produces a negative regulator of ecto-5'-nucleotidase (CD73).

Snider NT, Altshuler PJ, Wan S, Welling TH, Cavalcoli J, Omary MB - Mol. Biol. Cell (2014)

The human NT5E gene is regulated by alternative splicing. (A) Species comparison of the number of NT5E predicted transcripts using the Ensembl database. (B) Human NT5E has five splice variants, all predicted to be protein coding (bp, base pairs; aa, amino acids), but only two are annotated by CCDS. (C) The CCDS-validated transcripts NT5E-001 (NT5E-1) and NT5E-201 (NT5E-2), which differ with respect to the presence of exon 7 (arrow) in NT5E-1, are shown schematically.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4263446&req=5

Figure 1: The human NT5E gene is regulated by alternative splicing. (A) Species comparison of the number of NT5E predicted transcripts using the Ensembl database. (B) Human NT5E has five splice variants, all predicted to be protein coding (bp, base pairs; aa, amino acids), but only two are annotated by CCDS. (C) The CCDS-validated transcripts NT5E-001 (NT5E-1) and NT5E-201 (NT5E-2), which differ with respect to the presence of exon 7 (arrow) in NT5E-1, are shown schematically.
Mentions: Using the Ensembl genome browser (Flicek et al., 2014), we compared the alternative splicing pattern of human NT5E to nine other vertebrate species. Whereas human NT5E encodes five transcripts, all other species, except for cow, are predicted to have one NT5E transcript (Figure 1A). Aside from NT5E-001, which encodes the full-length canonical CD73 protein, NT5E-201 (Figure 1B) is the only other human transcript annotated by the Collaborative Consensus Coding Sequence (CCDS) project (Harte et al., 2012) as being highly likely to encode a protein. Therefore we focused our subsequent analysis on comparing these two transcripts, and we refer to NT5E-001 and NT5E-201 as NT5E-1 and NT5E-2, respectively. The only difference between the two transcripts is the absence of exon 7 in NT5E-2 (Figure 1C).

Bottom Line: The two human isoforms exhibited functional differences, such that ectopic expression of canonical CD73 (CD73L) in human HepG2 cells was associated with decreased expression of the proliferation marker Ki67, whereas CD73S expression did not have an effect on Ki67 expression.Furthermore, CD73S complexed with CD73L and promoted proteasome-dependent CD73L degradation.The findings reveal species-specific CD73 regulation, with potential significance to cancer, fibrosis, and other diseases characterized by changes in CD73 expression and function.

View Article: PubMed Central - PubMed

Affiliation: Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109.

Show MeSH
Related in: MedlinePlus