Speaker：HE Chuan, Ph.D.

                  University of Chicago

Time：10:30-12:00 AM Aug 31

Location: First-floor, Conference Room, BIG, CAS

Abstract:

Reversible chemical modifications on nucleic acids and proteins play critical roles in biological 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. I will present chemical strategies we have developed to enrich, sequence, and study novel nucleic acid modifications that include 5-hydroxymethylcytosine and its further oxidized forms in mammalian genome. Prior to our work, no example of reversible chemical modifications on RNA that could affect gene expression had been shown. We have discovered the first two RNA demethylases: FTO, a protein associated with human fat mass obesity, and ALKBH5, a protein that affects spermatogenesis in a mouse model. 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 studies provide the first demonstration of reversible RNA modification that may impact biological regulation analogous to the well-known reversible DNA and histone chemical modifications. We have also discovered proteins that can selectively recognize m6A-modified mRNA and affect the translation status and lifetime of the target mRNA. These discoveries indicate the presence of a new mode of biological regulation that depends on reversible RNA modification.