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Effect of mutations on the p53 IRES RNA structure Implications for de-regulation of the synthesis of p53 isoforms

Grover, Richa and Sharathchandra, Arandkar and Ponnuswamy, Anand and Khan, Debjit and Das, Saumitra (2011) Effect of mutations on the p53 IRES RNA structure Implications for de-regulation of the synthesis of p53 isoforms. In: RNA Biology, 8 (1). pp. 132-142.

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Official URL: http://www.landesbioscience.com/journals/rnabiolog...

Abstract

Earlier we have demonstrated the presence of internal ribosome entry site (IRES) within tumor suppressor p53 mRNA. Here we have mapped the putative secondary structure of p53-IRES RNA using information from chemical probing and nuclease mapping experiments. Additionally, the secondary structure of the IRES element of the wild-type RNA was compared with cancer-derived silent mutant p53 RNAs. These mutations might result in the conformational alterations of p53-IRES RNAs. The results also indicate decreased IRES activities of the mutants as compared to wild-type RNA. Further, it was observed that some of the cytoplasmic trans-acting factors, critical for enhancing IRES function, were unable to bind mutant RNAs as efficiently as to wild-type. Our results suggest that hnRNP C1/C2 binds to p53-IRES and siRNA mediated partial silencing of hnRNP C1/C2 showed appreciable decrease in IRES function and consequent decrease in the level of the corresponding p53 isoform. Interestingly mutant p53 IRES showed lesser binding with hnRNP C1/C2 protein. Finally, upon doxorubicin treatment, the mutant RNAs were unable to show enhanced p53 synthesis to similar extent compared to wild type. Taken together, these observations suggest that mutations occurring in the p53 IRES might have profound implications for de-regulation of its expression and activity.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to Landes Bioscience.
Keywords: p53mRNA;regulation of p53 isoforms;IRES RNA secondary structure;IRES trans acting factors
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 12 Apr 2011 10:26
Last Modified: 12 Apr 2011 10:26
URI: http://eprints.iisc.ernet.in/id/eprint/36565

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