Control of HuR Expression by MicroRNA and Auto-Regulatory Mechanism

Guha, Abhishek (2013) Control of HuR Expression by MicroRNA and Auto-Regulatory Mechanism. Masters thesis, Indian Institute of Science Education and Research Kolkata.

PDF (MS Dissertation of Abhishek Guha (11IP04)) Abhishek_Guha-11IP04-MSThesis.pdf - Submitted Version Restricted to Repository staff only Download (1MB)

Abstract

RNA binding protein HuR and microRNA miR-125b antagonistically regulate p53 translation. HuR enhances p53 translation in response to DNA damage caused by UVirradiation, whereas DNA damage can also upregulate p53 level directly by stabilizing the protein post-translationally. Thus, these interactions form a coherent feed forward loop that upregulates p53 translation. On the other hand, miR-125b downregulates p53 translation and we have shown it can also inhibit HuR translation to keep the p53 level low. Therefore, an incoherent feed forward loop is formed that downregulates p53 translation. We have also shown HuR can bind to 3’-UTR of its own mRNA and enhances translation. It can also rescue miR-125b-mediated downregulation of HuR mRNA translation, thereby indicating a positive autoregulation of HuR expression. Thus, all these coherent feed forward, incoherent feed forward and positive auto-regulatory loops finally form a network around the RNA binding protein HuR which regulate the intracellular p53 level.

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