ELUCIDATING THE DIRECT ROLE OF M6A IN THE HUMAN TRANSCRIPTOME

The best characterized and most abundant internal RNA modification is the methylation of adenosine at position 6 to give N6-methyladenosine (m6A). m6A modification on cellular RNAs was discovered in the 1970s. The past decade has witnessed major progress that illustrated important roles of this mark in various aspects of gene control. Due to its pleiotropic roles, the direct effect of m6A regulation of gene expression has remained incompletely understood. Traditional methods of understanding protein function, like CRISPR/Cas9 and RNA interference, have many limitations and have halted the process of fully understanding the direct functions of m6A. Here, we attempt alternative approaches that avoid the challenges of protein silencing through genomic alterations or transcript inhibition, but rather we focus on the direct targeting of proteins for degradation and rapid chemical inhibition of the m6A methyltransferase in a human cell model HCT116. This study allows for the direct analysis of the m6A modification in RNA regulation in both the native state and upon signaling induction