Reversible chemical modifications on nucleic acids and proteins play critical roles in gene expression regulation. The five bases that comprise nucleic acids - adenine, guanine, cytosine, thymine, and uracil - can be chemically and enzymatically modified. These chemical events can have significant biological consequences, particularly for gene expression. Prior to our work, no example of reversible chemical modifications on RNA that could affect gene expression had been shown. Together with our colleagues we have discovered the first two RNA demethylases: FTO and ALKBH5. These two proteins catalyze oxidative demethylation of the most prevalent internal modifications of mammalian messenger RNA (mRNA) and other nuclear RNA, N6-methyladenosine (m6A). These results indicate that reversible RNA modification could impact biological regulation analogous to the well-known reversible DNA and histone chemical modifications. We have also identified and characterized proteins that can selectively recognize m6A-modified mRNA; these m6A reader proteins affect the translation status and lifetime of the target mRNA. We have also characterized molecular machines that deposit the m6A methylation on nuclear RNA. Our discoveries indicate the presence of a new mode of biological regulation that depends on reversible RNA modification.

Reversible RNA methylation in biological regulation

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.