Identification of TINO
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 3â²-untranslated region of BCL-2 mRNA contains an ARE that accounts for rapid BCL-2 do...
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Published in | The Journal of biological chemistry Vol. 279; no. 19; pp. 20154 - 20166 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
American Society for Biochemistry and Molecular Biology
07.05.2004
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Online Access | Get full text |
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Summary: | 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 3â²-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. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M314071200 |