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High-dose siRNAs upregulate mouse Eri-1 at both transcription and posttranscription levels.

Bian Y, Zhou W, Zhao Y, Li X, Geng W, Hao R, Yang Q, Huang W - PLoS ONE (2011)

Bottom Line: High-dose siRNAs (hd-siRNAs) can enhance Eri-1 expression, which in return degrade siRNAs and greatly reduces RNAi efficiency.In addition, hd-siRNAs also abolish the 3' untranslated region (UTR) mediated posttranscriptional repression of meri-1.Our findings demonstrate the molecular mechanism underlying the upregulation of meri-1 by hd-siRNA.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, School of Life Science, Fudan University, Shanghai, China.

ABSTRACT
The eri-1 gene encodes a 3' exonuclease that can negatively regulate RNA interference via siRNase activity. High-dose siRNAs (hd-siRNAs) can enhance Eri-1 expression, which in return degrade siRNAs and greatly reduces RNAi efficiency. Here we report that hd-siRNAs induce mouse Eri-1 (meri-1) expression through the recruitment of Sp1, Ets-1, and STAT3 to the meri-1 promoter and the formation of an Sp1-Ets-1-STAT3 complex. In addition, hd-siRNAs also abolish the 3' untranslated region (UTR) mediated posttranscriptional repression of meri-1. Our findings demonstrate the molecular mechanism underlying the upregulation of meri-1 by hd-siRNA.

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Schematic summary of the hd-siRNA-stimulated meri-1 promoter activity.High-dose siRNAs treatment induces the interaction of Sp1 with histone acetyltransferase (HAT) leading to the acetylation of Sp1 and the DNA binding of Sp1 to the meri-1 promoter. In addition, histone deacetylases (HDAC) are released from the promoter. STAT3 will be recruited to the meri-1 promoter and bridge Sp1 with the co-activator Ets-1 to form the transcriptional complex and enhance the transcription of meri-1.
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pone-0026466-g007: Schematic summary of the hd-siRNA-stimulated meri-1 promoter activity.High-dose siRNAs treatment induces the interaction of Sp1 with histone acetyltransferase (HAT) leading to the acetylation of Sp1 and the DNA binding of Sp1 to the meri-1 promoter. In addition, histone deacetylases (HDAC) are released from the promoter. STAT3 will be recruited to the meri-1 promoter and bridge Sp1 with the co-activator Ets-1 to form the transcriptional complex and enhance the transcription of meri-1.

Mentions: In conclusion, as shown in Figure 7, we propose that, in response to hd-siRNA treatment, Sp1 interacts with histone acetyltransferases (HAT) leading to the acetylation of Sp1 and the DNA binding of Sp1 to the meri-1 promoter. This occurs in conjunction with release of HDACs from the promoter. Then, STAT3 is recruited to the meri-1 promoter and bridges Sp1 with the co-activator Ets-1 to form the transcriptional complex and elevate the level of gene transcription.


High-dose siRNAs upregulate mouse Eri-1 at both transcription and posttranscription levels.

Bian Y, Zhou W, Zhao Y, Li X, Geng W, Hao R, Yang Q, Huang W - PLoS ONE (2011)

Schematic summary of the hd-siRNA-stimulated meri-1 promoter activity.High-dose siRNAs treatment induces the interaction of Sp1 with histone acetyltransferase (HAT) leading to the acetylation of Sp1 and the DNA binding of Sp1 to the meri-1 promoter. In addition, histone deacetylases (HDAC) are released from the promoter. STAT3 will be recruited to the meri-1 promoter and bridge Sp1 with the co-activator Ets-1 to form the transcriptional complex and enhance the transcription of meri-1.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198429&req=5

pone-0026466-g007: Schematic summary of the hd-siRNA-stimulated meri-1 promoter activity.High-dose siRNAs treatment induces the interaction of Sp1 with histone acetyltransferase (HAT) leading to the acetylation of Sp1 and the DNA binding of Sp1 to the meri-1 promoter. In addition, histone deacetylases (HDAC) are released from the promoter. STAT3 will be recruited to the meri-1 promoter and bridge Sp1 with the co-activator Ets-1 to form the transcriptional complex and enhance the transcription of meri-1.
Mentions: In conclusion, as shown in Figure 7, we propose that, in response to hd-siRNA treatment, Sp1 interacts with histone acetyltransferases (HAT) leading to the acetylation of Sp1 and the DNA binding of Sp1 to the meri-1 promoter. This occurs in conjunction with release of HDACs from the promoter. Then, STAT3 is recruited to the meri-1 promoter and bridges Sp1 with the co-activator Ets-1 to form the transcriptional complex and elevate the level of gene transcription.

Bottom Line: High-dose siRNAs (hd-siRNAs) can enhance Eri-1 expression, which in return degrade siRNAs and greatly reduces RNAi efficiency.In addition, hd-siRNAs also abolish the 3' untranslated region (UTR) mediated posttranscriptional repression of meri-1.Our findings demonstrate the molecular mechanism underlying the upregulation of meri-1 by hd-siRNA.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, School of Life Science, Fudan University, Shanghai, China.

ABSTRACT
The eri-1 gene encodes a 3' exonuclease that can negatively regulate RNA interference via siRNase activity. High-dose siRNAs (hd-siRNAs) can enhance Eri-1 expression, which in return degrade siRNAs and greatly reduces RNAi efficiency. Here we report that hd-siRNAs induce mouse Eri-1 (meri-1) expression through the recruitment of Sp1, Ets-1, and STAT3 to the meri-1 promoter and the formation of an Sp1-Ets-1-STAT3 complex. In addition, hd-siRNAs also abolish the 3' untranslated region (UTR) mediated posttranscriptional repression of meri-1. Our findings demonstrate the molecular mechanism underlying the upregulation of meri-1 by hd-siRNA.

Show MeSH