Identification of TINO: A new evolutionarily conserved BCL-2 AU-rich element RNA-binding protein

Martino Donnini, Andrea Lapucci, Laura Papucci, Ewa Witort, Alain Jacquier, Gary Brewer, Angelo Nicolin, Sergio Capaccioli, Nicola Schiavone

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Abstract

Modulation of mRNA stability by regulatory cis-acting AU-rich elements (AREs) and ARE-binding proteins is an important posttranscriptional mechanism of gene expression control. We previously demonstrated that the 3′-untranslated region of BCL-2 mRNA contains an ARE that accounts for rapid BCL-2 down-regulation in response to apoptotic stimuli. We also demonstrated that the BCL-2 ARE core interacts with a number of ARE-binding proteins, one of which is AU-rich factor 1/heterogeneous nuclear ribonucleoprotein D, known for its interaction with mRNA elements of others genes. In an attempt to search for other BCL-2 mRNA-binding proteins, we used the yeast RNA three-hybrid system assay and identified a novel human protein that interacts with BCL-2 ARE. We refer to it as TINO. The predicted protein sequence of TINO reveals two amino-terminal heterogeneous nuclear ribonucleoprotein K homology motifs for nucleic acid binding and a carboxyl-terminal RING domain, endowed with a putative E3 ubiquitin-protein ligase activity. In addition the novel protein is evolutionarily conserved; the two following orthologous proteins have been identified with protein-protein BLAST: posterior end mark-3 (PEM-3) of Ciona savignyi and muscle excess protein-3 (MEX-3) of Caenorhabditis elegans. Upon binding, TINO destabilizes a chimeric reporter construct containing the BCL-2 ARE sequence, revealing a negative regulatory action on BCL-2 gene expression at the posttranscriptional level.

Original languageEnglish (US)
Pages (from-to)20154-20166
Number of pages13
JournalJournal of Biological Chemistry
Volume279
Issue number19
DOIs
StatePublished - May 7 2004

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Donnini, M., Lapucci, A., Papucci, L., Witort, E., Jacquier, A., Brewer, G., Nicolin, A., Capaccioli, S., & Schiavone, N. (2004). Identification of TINO: A new evolutionarily conserved BCL-2 AU-rich element RNA-binding protein. Journal of Biological Chemistry, 279(19), 20154-20166. https://doi.org/10.1074/jbc.M314071200