STRUCTURAL AND MECHANISTIC STUDIES OF NUCLEIC ACID DEMETHYLASE FTO

Abstract

FTO gene was the first gene that provided the strongest direct link to obesity uncovered by GWAS. Functional FTO is crucial for normal growth and development. FTO is an m6A demethylase and m6A occurred within a consensus sequence in mRNA. The status of m6A in RNA transcripts can affect RNA splicing, translation and degradation, leading to the conclusion that m6A is involved in epigenetic regulation at the RNA level. There are two m6A demethylases known so far, FTO and ALKBH5 and they have very different biological roles. It is not clear how FTO is selectively expressed over ALKBH5 and how FTO regulate the RNA methylation status in vivo. Thus, in this thesis, we present our mechanistic and structural studies of FTO which aid toward the elucidation of FTO roles and functions.