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REGULATION OF THE MYC PROTO-ONCOGENE BY RNA BINDING PROTEINS AND MIRNAS

by
Patricia Irizarry Barreto
B.S., University of Puerto Rico-Mayaguez - 2003

Thesis Advisor: Gary Brewer, Ph.D.
Graduate Program Molecular Genetics, Microbiology & Immunology

RWJMS Research Tower
7th floor Conference Room
Piscataway

Thursday, December 15, 2011
10:00 a.m.


Abstract

MicroRNAs (miRNAs) and AU binding proteins (AUBPs) are post-translational regulators that bind to the 3’UTR of target mRNA to control genetic expression by binding to the miRNA recognition elements (MREs) and the AU rich element (ARE), respectively. Here we explored the role of three conserved regions at the MYC 3’UTR, known as Boxes A, B and C. Luciferase assays revealed that the three regions act as binding sites for repressors of MYC translation. One of these conserved regions (Box B) is a validated MRE and another one (BoxC) is within an ARE. We showed that two AUBPs, HuR and AUF1, affected miRNA association to the MYC 3’UTR. Altering association of HuR with the MYC mRNA reduced association of miRNAs with the MYC 3’UTR, while altering association of AUF1 with the MYC mRNA resulted in an increase in miRNA association with the MYC 3’UTR. Our observations suggest a model where AUF1 and HuR exert opposite effects in miRNA association with the MYC mRNA, controlling MYC genetic expression.


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