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 knockdown reduced the expression of endogenous bcl-2, whereas 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 the 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 the 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: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 284:31(2009 Jul 31), pp. 20946-20955.
|Titolo:||B cell lymphoma (Bcl)-2 protein is the major determinant in bcl-2 adenine-uridine-rich element turnover overcoming HuR activity|
GHISOLFI, LAURA (Primo)
CALASTRETTI, ANGELA LUISA (Secondo)
NICOLIN, ANGELO NICOLO' (Penultimo)
BEVILACQUA, ANNAMARIA (Ultimo)
|Parole Chiave:||B-Cell Lymphoma ; Bcl-2mRNA ; Binding proteins ; Data support ; Decay kinetics ; Dose-dependent ; Genetic backgrounds ; Human cell lines ; Living cell ; Luciferase reporter system ; Molecular mechanism ; Post-transcriptional regulations ; Untranslated regions|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
Settore BIO/11 - Biologia Molecolare
Settore BIO/13 - Biologia Applicata
|Data di pubblicazione:||31-lug-2009|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1074/jbc.M109.023721|
|Appare nelle tipologie:||01 - Articolo su periodico|