TAILIEUCHUNG - Báo cáo khoa học: Regulation of translational efficiency by different splice variants of the Disc large 1 oncosuppressor 5¢-UTR

Human Disc large (DLG1) has been demonstrated to be involved in the control of cell polarity and maintenance of tissue architecture, and is fre-quently lost in human tumours. However, the mechanisms controlling DLG1 expression are poorly understood. | IFEBS Journal Regulation of translational efficiency by different splice variants of the Disc large 1 oncosuppressor 5 -UTR Ana L. Cavatorta1 Florencia Facciuto1 Marina Bugnon Valdano1 Federico Marziali1 Adriana A. Giri1 Lawrence Banks2 and Daniela Gardiol1 1 Institute de Biologia Molecular y Celular de Rosario - CONICET Facultad de Ciencias Bioquimicas y Farmaceuticas Rosario Argentina 2 InternationalCentre for Genetic Engineering and Biotechnology Trieste Italy Keywords cancer DLG1 polarity translation regulation 5 -UTR Correspondence D. Gardiol IBR-CONICET Facultad de Ciencias Bioquimicas y Farmaceuticas Suipacha 531 2000 Rosario Argentina Fax 54 341 4390645 Tel 54 341 4350661 E-mail gardiol@ Received 23 January 2011 revised 1 May 2011 accepted 17 May 2011 doi Human Disc large DLG1 has been demonstrated to be involved in the control of cell polarity and maintenance of tissue architecture and is frequently lost in human tumours. However the mechanisms controlling DLG1 expression are poorly understood. To further examine the regulation of DLG1 expression we analysed the 5 ends of DLG1 transcripts by rapid amplification of cDNA ends polymerase chain reaction. We identified an alternative splicing event in the 5 region of DLG1 mRNA that generates transcripts with two different 5 untranslated regions 5 -UTRs . We show by reporter assays that the DLG1 5 -UTR containing an alternatively spliced exon interferes with the translation of a downstream open reading frame ORF . However no significant differences in mRNA stability among the DLG1 5 -UTR variants were observed. Sequence analysis of the additional exon present in the larger DLG1 5 -UTR showed the presence of an upstream short ORF which is lost in the short version of the 5 -UTR DLG1. By mutagenesis and luciferase assays we analysed the contribution of this upstream short ORF in reducing translation efficiency and showed that its disruption can revert to some extent the .

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