Resveratrol, by modulating RNA processing factor levels, can influence the alternative splicing of pre-mRNAs.

Alternative pre-mRNA splicing defects can contribute to, or result from, various diseases, including cancer. Aberrant mRNAs, splicing factors and other RNA processing factors have therefore become targets for new therapeutic interventions. Here we report that the natural polyphenol resveratrol can m...

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Autores principales:	M Andrea Markus, Francine Z Marques, Brian J Morris
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/37ad2a27095b42f98805d70810543c20
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spelling	oai:doaj.org-article:37ad2a27095b42f98805d70810543c202021-11-18T07:32:27ZResveratrol, by modulating RNA processing factor levels, can influence the alternative splicing of pre-mRNAs.1932-620310.1371/journal.pone.0028926https://doaj.org/article/37ad2a27095b42f98805d70810543c202011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22174926/?tool=EBIhttps://doaj.org/toc/1932-6203Alternative pre-mRNA splicing defects can contribute to, or result from, various diseases, including cancer. Aberrant mRNAs, splicing factors and other RNA processing factors have therefore become targets for new therapeutic interventions. Here we report that the natural polyphenol resveratrol can modulate alternative splicing in a target-specific manner. We transfected minigenes of several alternatively spliceable primary mRNAs into HEK293 cells in the presence or absence of 1, 5, 20 and 50 µM resveratrol and measured exon levels by semi-quantitative PCR after separation by agarose gel electrophoresis. We found that 20 µg/ml and 50 µg/ml of resveratrol affected exon inclusion of SRp20 and SMN2 pre-mRNAs, but not CD44v5 or tau pre-mRNAs. By Western blotting and immunofluorescence we showed that this effect may be due to the ability of resveratrol to change the protein level but not the localization of several RNA processing factors. The processing factors that increased significantly were ASF/SF2, hnRNPA1 and HuR, but resveratrol did not change the levels of RBM4, PTBP1 and U2AF35. By means of siRNA-mediated knockdown we depleted cells of SIRT1, regarded as a major target of resveratrol, and showed that the effect on splicing was not dependent on SIRT1. Our results suggest that resveratrol might be an attractive small molecule to treat diseases in which aberrant splicing has been implicated, and justify more extensive research on the effects of resveratrol on the splicing machinery.M Andrea MarkusFrancine Z MarquesBrian J MorrisPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e28926 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q M Andrea Markus Francine Z Marques Brian J Morris Resveratrol, by modulating RNA processing factor levels, can influence the alternative splicing of pre-mRNAs.
description	Alternative pre-mRNA splicing defects can contribute to, or result from, various diseases, including cancer. Aberrant mRNAs, splicing factors and other RNA processing factors have therefore become targets for new therapeutic interventions. Here we report that the natural polyphenol resveratrol can modulate alternative splicing in a target-specific manner. We transfected minigenes of several alternatively spliceable primary mRNAs into HEK293 cells in the presence or absence of 1, 5, 20 and 50 µM resveratrol and measured exon levels by semi-quantitative PCR after separation by agarose gel electrophoresis. We found that 20 µg/ml and 50 µg/ml of resveratrol affected exon inclusion of SRp20 and SMN2 pre-mRNAs, but not CD44v5 or tau pre-mRNAs. By Western blotting and immunofluorescence we showed that this effect may be due to the ability of resveratrol to change the protein level but not the localization of several RNA processing factors. The processing factors that increased significantly were ASF/SF2, hnRNPA1 and HuR, but resveratrol did not change the levels of RBM4, PTBP1 and U2AF35. By means of siRNA-mediated knockdown we depleted cells of SIRT1, regarded as a major target of resveratrol, and showed that the effect on splicing was not dependent on SIRT1. Our results suggest that resveratrol might be an attractive small molecule to treat diseases in which aberrant splicing has been implicated, and justify more extensive research on the effects of resveratrol on the splicing machinery.
format	article
author	M Andrea Markus Francine Z Marques Brian J Morris
author_facet	M Andrea Markus Francine Z Marques Brian J Morris
author_sort	M Andrea Markus
title	Resveratrol, by modulating RNA processing factor levels, can influence the alternative splicing of pre-mRNAs.
title_short	Resveratrol, by modulating RNA processing factor levels, can influence the alternative splicing of pre-mRNAs.
title_full	Resveratrol, by modulating RNA processing factor levels, can influence the alternative splicing of pre-mRNAs.
title_fullStr	Resveratrol, by modulating RNA processing factor levels, can influence the alternative splicing of pre-mRNAs.
title_full_unstemmed	Resveratrol, by modulating RNA processing factor levels, can influence the alternative splicing of pre-mRNAs.
title_sort	resveratrol, by modulating rna processing factor levels, can influence the alternative splicing of pre-mrnas.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/37ad2a27095b42f98805d70810543c20
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Resveratrol, by modulating RNA processing factor levels, can influence the alternative splicing of pre-mRNAs.

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