IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
artículos
Título:
Regulation of translational efficiency by different splice variants of the Disc Large 1 oncosupressor 5´-UTR
Autor/es:
ANA L. CAVATORTA, FLORENCIA FACCIUTO, MARINA BUGNON VALDANO, FEDERICO MARZIALI, ADRIANA A. GIRI, LAWRENCE BANKS AND DANIELA GARDIOL
Revista:
FEBS JOURNAL
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Lugar: Cambridge; Año: 2011 vol. 278 p. 2596 - 2608
ISSN:
1742-464X
Resumen:
Human Disc large (DLG1) has been demonstrated to be involved in thecontrol of cell polarity and maintenance of tissue architecture, and is frequentlylost in human tumours. However, the mechanisms controllingDLG1 expression are poorly understood. To further examine the regulationof DLG1 expression, we analysed the 5´ ends of DLG1 transcripts by rapidamplification of cDNA ends polymerase chain reaction. We identified analternative splicing event in the 5´ region of DLG1 mRNA that generatestranscripts with two different 5´ untranslated regions (5´UTRs). We showby reporter assays that the DLG1 5¢-UTR containing an alternativelyspliced exon interferes with the translation of a downstream open readingframe (ORF). However, no significant differences in mRNA stabilityamong the DLG1 5´UTR variants were observed. Sequence analysis of theadditional exon present in the larger DLG1 5´UTR showed the presenceof an upstream short ORF which is lost in the short version of the 5´UTRDLG1. By mutagenesis and luciferase assays, we analysed the contributionof this upstream short ORF in reducing translation efficiency, and showedthat its disruption can revert, to some extent, the negative regulation oflarge 5´UTR. Using computational modelling we also show that the largeDLG1 5´UTR isoform forms a more stable structure than the short version,and this may contribute to its ability to repress translation. This representsthe first analysis of the 5´ region of the DLG1 transcripts andshows that differential expression of alternatively spliced 5´UTRs with differenttranslational properties could result in changes in DLG1 abundance.