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miR-503 represses CUG-binding protein 1 translation by recruiting CUGBP1 mRNA to processing bodies
microRNAs (miRNAs) and RNA-binding proteins (RBPs) jointly regulate gene expression at the posttranscriptional level and are involved in many aspects of cellular functions. The RBP CUG-binding protein 1 (CUGBP1) destabilizes and represses the translation of several target mRNAs, but the exact mechan...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248894/ https://www.ncbi.nlm.nih.gov/pubmed/22072795 http://dx.doi.org/10.1091/mbc.E11-05-0456 |
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author | Cui, Yu-Hong Xiao, Lan Rao, Jaladanki N. Zou, Tongtong Liu, Lan Chen, Yu Turner, Douglas J. Gorospe, Myriam Wang, Jian-Ying |
author_facet | Cui, Yu-Hong Xiao, Lan Rao, Jaladanki N. Zou, Tongtong Liu, Lan Chen, Yu Turner, Douglas J. Gorospe, Myriam Wang, Jian-Ying |
author_sort | Cui, Yu-Hong |
collection | PubMed |
description | microRNAs (miRNAs) and RNA-binding proteins (RBPs) jointly regulate gene expression at the posttranscriptional level and are involved in many aspects of cellular functions. The RBP CUG-binding protein 1 (CUGBP1) destabilizes and represses the translation of several target mRNAs, but the exact mechanism that regulates CUGBP1 abundance remains elusive. In this paper, we show that miR-503, computationally predicted to associate with three sites of the CUGBP1 mRNA, represses CUGBP1 expression. Overexpression of an miR-503 precursor (pre-miR-503) reduced the de novo synthesis of CUGBP1 protein, whereas inhibiting miR-503 by using an antisense RNA (antagomir) enhanced CUGBP1 biosynthesis and elevated its abundance; neither intervention changed total CUGBP1 mRNA levels. Studies using heterologous reporter constructs revealed a greater repressive effect of miR-503 through the CUGBP1 coding region sites than through the single CUGBP1 3′-untranslated region target site. CUGBP1 mRNA levels in processing bodies (P-bodies) increased in cells transfected with pre-miR-503, while silencing P-body resident proteins Ago2, RCK, or LSm4 decreased miR-503–mediated repression of CUGBP1 expression. Decreasing the levels of cellular polyamines reduced endogenous miR-503 levels and promoted CUGBP1 expression, an effect that was prevented by ectopic miR-503 overexpression. Repression of CUGBP1 by miR-503 in turn altered the expression of CUGBP1 target mRNAs and thus increased the sensitivity of intestinal epithelial cells to apoptosis. These findings identify miR-503 as both a novel regulator of CUGBP1 expression and a modulator of intestinal epithelial homoeostasis. |
format | Online Article Text |
id | pubmed-3248894 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-32488942012-03-16 miR-503 represses CUG-binding protein 1 translation by recruiting CUGBP1 mRNA to processing bodies Cui, Yu-Hong Xiao, Lan Rao, Jaladanki N. Zou, Tongtong Liu, Lan Chen, Yu Turner, Douglas J. Gorospe, Myriam Wang, Jian-Ying Mol Biol Cell Articles microRNAs (miRNAs) and RNA-binding proteins (RBPs) jointly regulate gene expression at the posttranscriptional level and are involved in many aspects of cellular functions. The RBP CUG-binding protein 1 (CUGBP1) destabilizes and represses the translation of several target mRNAs, but the exact mechanism that regulates CUGBP1 abundance remains elusive. In this paper, we show that miR-503, computationally predicted to associate with three sites of the CUGBP1 mRNA, represses CUGBP1 expression. Overexpression of an miR-503 precursor (pre-miR-503) reduced the de novo synthesis of CUGBP1 protein, whereas inhibiting miR-503 by using an antisense RNA (antagomir) enhanced CUGBP1 biosynthesis and elevated its abundance; neither intervention changed total CUGBP1 mRNA levels. Studies using heterologous reporter constructs revealed a greater repressive effect of miR-503 through the CUGBP1 coding region sites than through the single CUGBP1 3′-untranslated region target site. CUGBP1 mRNA levels in processing bodies (P-bodies) increased in cells transfected with pre-miR-503, while silencing P-body resident proteins Ago2, RCK, or LSm4 decreased miR-503–mediated repression of CUGBP1 expression. Decreasing the levels of cellular polyamines reduced endogenous miR-503 levels and promoted CUGBP1 expression, an effect that was prevented by ectopic miR-503 overexpression. Repression of CUGBP1 by miR-503 in turn altered the expression of CUGBP1 target mRNAs and thus increased the sensitivity of intestinal epithelial cells to apoptosis. These findings identify miR-503 as both a novel regulator of CUGBP1 expression and a modulator of intestinal epithelial homoeostasis. The American Society for Cell Biology 2012-01-01 /pmc/articles/PMC3248894/ /pubmed/22072795 http://dx.doi.org/10.1091/mbc.E11-05-0456 Text en © 2012 Cui et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Cui, Yu-Hong Xiao, Lan Rao, Jaladanki N. Zou, Tongtong Liu, Lan Chen, Yu Turner, Douglas J. Gorospe, Myriam Wang, Jian-Ying miR-503 represses CUG-binding protein 1 translation by recruiting CUGBP1 mRNA to processing bodies |
title | miR-503 represses CUG-binding protein 1 translation by recruiting CUGBP1 mRNA to processing bodies |
title_full | miR-503 represses CUG-binding protein 1 translation by recruiting CUGBP1 mRNA to processing bodies |
title_fullStr | miR-503 represses CUG-binding protein 1 translation by recruiting CUGBP1 mRNA to processing bodies |
title_full_unstemmed | miR-503 represses CUG-binding protein 1 translation by recruiting CUGBP1 mRNA to processing bodies |
title_short | miR-503 represses CUG-binding protein 1 translation by recruiting CUGBP1 mRNA to processing bodies |
title_sort | mir-503 represses cug-binding protein 1 translation by recruiting cugbp1 mrna to processing bodies |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248894/ https://www.ncbi.nlm.nih.gov/pubmed/22072795 http://dx.doi.org/10.1091/mbc.E11-05-0456 |
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