Secretariat, Alumni Association, IDAC
Date	Thursday, 7 March 2024, 13:00～14:00
Room	7th Floor, Seminar Room 1,IDAC Center for Basic Aging Research
Title	m6A and pseudouridine (Ψ) in vertebrate mRNA.
Speaker	Professor. Dr. Sabastian Leidel
Affiliation	Research Group for RNA Biochemistry Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) University of Bern Hochschulstrasse 6, Bern, Canton of Bern, 3012, Switzerland
Organizer	FANYAN WEI (Dept. Modomics Biology and Medicine, ext. 8562)
Abstract	Chemical RNA modifications affect all aspects of RNA biology, including biogenesis, turnover, and tuning the interactions of RNA molecules. I will present two current stories from my lab involving mRNA and tRNA modifications. First, in collaboration with Sebastian Glatt’s group (Krakow, Poland), we solved the structure of human PUS3 and performed several biochemical assays to understand how the absence of Ψ is associated with disease. Interestingly, our findings strongly argue against a role of PUS3 in mRNA modification, but reveal how the highly conserved PUS3 ensures target specificity. Second, to understand the role of N6-methyladenosine (m6A) during vertebrate development, we deleted Mettl3 in zebrafish. mettl3-/- fish die within the first month after fertilization. We combined RNA-seq and single-cell RNA-seq of Mettl3-/- mutant heads to analyze the molecular phenotypes. Strikingly, genes associated with eye disease are dysregulated and histological analysis revealed significant morphological changes of the mutant retinas, while electroretinography uncovered visual defects. Furthermore, mettl3-/- mutants displayed defects in locomotor activity in automated dark-light transition experiments, a phenotype that worsened over time. Finally, we found that mutant cells respond to the lack of m6A by regulating the splicing of wtap, the scaffold member of the m6A-writer complex.