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This Article Full Text Free Full Text (PDF) Free All Versions of this Article: fj.08-113902v1 23/1/172    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Errasti-Murugarren, E. Articles by Pastor-Anglada, M. Search for Related Content PubMed PubMed Citation Articles by Errasti-Murugarren, E. Articles by Pastor-Anglada, M.

A splice variant of the SLC28A3 gene encodes a novel human concentrative nucleoside transporter-3 (hCNT3) protein localized in the endoplasmic reticulum

Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Institut de Biomedicina, CIBER EHD, Universitat de Barcelona, Barcelona, Spain

³ Correspondence: Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Avda Diagonal, 645 E-08028 Barcelona, Spain. E-mail: mpastor{at}ub.edu

Nucleoside transporters are plasma membrane proteins essential for nucleoside salvage. Among them, human concentrative nucleoside transporter 3 (hCNT3, SLC28A3) plays an essential role in this process because of its broader substrate selectivity and higher concentrative ability than the other members of the SLC28 protein family, hCNT1 and hCNT2. The aim of this study was to characterize an isoform of hCNT3, encoded by an alternatively spliced SLC28A3-related mRNA, the first identified for a CNT protein. This variant, named hCNT3ins, is the result of the insertion of 176 bp corresponding to an intron located between exons 2 and 3 of the gene. This insertion results in a shift of the reading frame, yielding a protein lacking 69 residues of the N terminus. hCNT3 and hCNT3ins mRNAs are simultaneously expressed both in normal and transformed cells and are differentially regulated by activation and differentiation. Because of the N-terminal deletion, hCNT3ins is retained in the endoplasmic reticulum, where it shows a typical hCNT3-related activity. hCNT3ins exhibits a shorter half-life than its plasma membrane counterpart, being degraded via a proteasome-dependent pathway. We suggest that this novel hCNT3 isoform would be involved in the salvage of intracellular nucleosides from the lumen of the endoplasmic reticulum to the cytoplasm.—Errasti-Murugarren, E., Molina-Arcas, M., Casado, F. J., Pastor-Anglada, M. A splice variant of the SLC28A3 gene encodes a novel human concentrative nucleoside transporter-3 (hCNT3) protein localized in the endoplasmic reticulum.

Key Words: alternative splicing • CNT • protein turnover