In the 3' untranslated region, the destabilizing adenine-uridine (AU)-rich elements (AREs) control the expression of several transcripts through interactions with ARE-binding proteins (AUBPs) and RNA degradation machinery. Although the fundamental role for AUBPs and associated factors in eliciting ARE-dependent degradation of cognate mRNAs has been recently highlighted, the molecular mechanisms underlying the specific regulation of individual mRNA turnover have not yet been fully elucidated. Here we focused on the post-transcriptional regulation of bcl-2 mRNA in human cell lines under different conditions and genetic backgrounds. In the context of an AUBPs silencing approach, HuR knock down reduced the expression of endogenous bcl-2 while, unexpectedly, a bcl-2 ARE-reporter transcript increased significantly, suggesting that HuR expression has opposite effects on endogenous and ectopic bcl-2 ARE. Moreover, evidence was provided for the essential, specific and dose-dependent role of Bcl-2 protein in regulating the decay kinetics of its own mRNA, as ascertained by a luciferase reporter system. Altogether, the data support a model whereby Bcl-2 protein is the major determinant of its own ARE-dependent transcript half-life in living cells and its effect overcomes the activity of ARE-binding proteins.

B cell lymphoma (Bcl)-2 protein is the major determinant in bcl-2 adenine-uridine-rich element turnover overcoming HuR activity / L.Ghisolfi; A.Calastretti; S.Franzi; G.Canti; M.Donnini; S.Capaccioli; A.Nicolin; A.Bevilacqua. - In: JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 1083-351X. - STAMPA. - 284(2009), pp. 20946-20955. [10.1074/jbc.M109.023721]

B cell lymphoma (Bcl)-2 protein is the major determinant in bcl-2 adenine-uridine-rich element turnover overcoming HuR activity

DONNINI, MARTINO;CAPACCIOLI, SERGIO;
2009

Abstract

In the 3' untranslated region, the destabilizing adenine-uridine (AU)-rich elements (AREs) control the expression of several transcripts through interactions with ARE-binding proteins (AUBPs) and RNA degradation machinery. Although the fundamental role for AUBPs and associated factors in eliciting ARE-dependent degradation of cognate mRNAs has been recently highlighted, the molecular mechanisms underlying the specific regulation of individual mRNA turnover have not yet been fully elucidated. Here we focused on the post-transcriptional regulation of bcl-2 mRNA in human cell lines under different conditions and genetic backgrounds. In the context of an AUBPs silencing approach, HuR knock down reduced the expression of endogenous bcl-2 while, unexpectedly, a bcl-2 ARE-reporter transcript increased significantly, suggesting that HuR expression has opposite effects on endogenous and ectopic bcl-2 ARE. Moreover, evidence was provided for the essential, specific and dose-dependent role of Bcl-2 protein in regulating the decay kinetics of its own mRNA, as ascertained by a luciferase reporter system. Altogether, the data support a model whereby Bcl-2 protein is the major determinant of its own ARE-dependent transcript half-life in living cells and its effect overcomes the activity of ARE-binding proteins.
284
20946
20955
L.Ghisolfi; A.Calastretti; S.Franzi; G.Canti; M.Donnini; S.Capaccioli; A.Nicolin; A.Bevilacqua
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2158/373622
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