A conserved stem loop motif in the 5'untranslated region regulates transforming growth factor-β(1) translation.

Transforming growth factor-β(1) (TGF-β(1)) regulates cellular proliferation, differentiation, migration, and survival. The human TGF-β(1) transcript is inherently poorly translated, and translational activation has been documented in relation to several stimuli. In this paper, we have sought to iden...

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Autores principales:	Robert H Jenkins, Rasha Bennagi, John Martin, Aled O Phillips, James E Redman, Donald J Fraser
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1ed840e9591c47239a98b5e940c3915d
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spelling	oai:doaj.org-article:1ed840e9591c47239a98b5e940c3915d2021-11-18T06:35:42ZA conserved stem loop motif in the 5'untranslated region regulates transforming growth factor-β(1) translation.1932-620310.1371/journal.pone.0012283https://doaj.org/article/1ed840e9591c47239a98b5e940c3915d2010-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20865036/?tool=EBIhttps://doaj.org/toc/1932-6203Transforming growth factor-β(1) (TGF-β(1)) regulates cellular proliferation, differentiation, migration, and survival. The human TGF-β(1) transcript is inherently poorly translated, and translational activation has been documented in relation to several stimuli. In this paper, we have sought to identify in cis regulatory elements within the TGF-β(1) 5'Untranslated Region (5'UTR). In silico analysis predicted formation of stable secondary structure in a G/C-rich element between nucleotides +77 to +106, and demonstrated that this element is highly conserved across species. Circular dichroism spectroscopy confirmed the presence of secondary structure in this region. The proximal 5'UTR was inhibitory to translation in reporter gene experiments, and mutation of the secondary structure motif increased translational efficiency. Translational regulation of TGF-β(1) mRNA is linked to altered binding of YB-1 protein to its 5'UTR. Immunoprecipitation-RT-qPCR demonstrated a high basal association of YB-1 with TGF-β(1) mRNA. However, mutation of the secondary structure motif did not prevent interaction of YB-1 with the 5'UTR, suggesting that YB-1 binds to this region due to its G/C-rich composition, rather than a specific, sequence-dependent, binding site. These data identify a highly conserved element within the TGF-β(1) 5'UTR that forms stable secondary structure, and is responsible for the inherent low translation efficiency of this cytokine.Robert H JenkinsRasha BennagiJohn MartinAled O PhillipsJames E RedmanDonald J FraserPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 8, p e12283 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Robert H Jenkins Rasha Bennagi John Martin Aled O Phillips James E Redman Donald J Fraser A conserved stem loop motif in the 5'untranslated region regulates transforming growth factor-β(1) translation.
description	Transforming growth factor-β(1) (TGF-β(1)) regulates cellular proliferation, differentiation, migration, and survival. The human TGF-β(1) transcript is inherently poorly translated, and translational activation has been documented in relation to several stimuli. In this paper, we have sought to identify in cis regulatory elements within the TGF-β(1) 5'Untranslated Region (5'UTR). In silico analysis predicted formation of stable secondary structure in a G/C-rich element between nucleotides +77 to +106, and demonstrated that this element is highly conserved across species. Circular dichroism spectroscopy confirmed the presence of secondary structure in this region. The proximal 5'UTR was inhibitory to translation in reporter gene experiments, and mutation of the secondary structure motif increased translational efficiency. Translational regulation of TGF-β(1) mRNA is linked to altered binding of YB-1 protein to its 5'UTR. Immunoprecipitation-RT-qPCR demonstrated a high basal association of YB-1 with TGF-β(1) mRNA. However, mutation of the secondary structure motif did not prevent interaction of YB-1 with the 5'UTR, suggesting that YB-1 binds to this region due to its G/C-rich composition, rather than a specific, sequence-dependent, binding site. These data identify a highly conserved element within the TGF-β(1) 5'UTR that forms stable secondary structure, and is responsible for the inherent low translation efficiency of this cytokine.
format	article
author	Robert H Jenkins Rasha Bennagi John Martin Aled O Phillips James E Redman Donald J Fraser
author_facet	Robert H Jenkins Rasha Bennagi John Martin Aled O Phillips James E Redman Donald J Fraser
author_sort	Robert H Jenkins
title	A conserved stem loop motif in the 5'untranslated region regulates transforming growth factor-β(1) translation.
title_short	A conserved stem loop motif in the 5'untranslated region regulates transforming growth factor-β(1) translation.
title_full	A conserved stem loop motif in the 5'untranslated region regulates transforming growth factor-β(1) translation.
title_fullStr	A conserved stem loop motif in the 5'untranslated region regulates transforming growth factor-β(1) translation.
title_full_unstemmed	A conserved stem loop motif in the 5'untranslated region regulates transforming growth factor-β(1) translation.
title_sort	conserved stem loop motif in the 5'untranslated region regulates transforming growth factor-β(1) translation.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/1ed840e9591c47239a98b5e940c3915d
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A conserved stem loop motif in the 5'untranslated region regulates transforming growth factor-β(1) translation.

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