Title

Characterization of a liver specific microRNA: miR-122

Date of Completion

January 2011

Keywords

Biology, Molecular|Biology, Genetics

Degree

Ph.D.

Abstract

microRNAs play a major role in regulation of gene expression at the post transcriptional level. They are able to bind a mRNA, usually in its 3' UTR and repress translation through a variety of mechanisms. Most microRNAs are expressed in a number of tissues, but there are some with very specific tissue expression. microRNA-122 (miR-122) is a highly abundant liver specific microRNA and plays a role in cholesterol biosynthesis, liver homeostasis, Hepatitis C Virus (HCV) replication, and hepatocellular carcinoma (HCC) progression. Inhibition of this microRNA reduces serum cholesterol by 40% in both mice and african green monkeys. Much has been uncovered as to the function of microRNAs through target mRNA identification, but little is known about the regulation of these microRNAs. This dissertation seeks to understand the mechanism which regulates the tissue specificity of miR-122 as well as the players involved. From our data, miR-122 is a liver specific microRNA that is regulated at the transcriptional level and is processed from a 6 kb primary transcript. We identified the core promoter and shown that it confers the tissue specificity and have identified possible transcription factors that play a role in enhancing miR-122 transcription. ^