RNA Epigenetics and Human Disease
Slot 1: Structural and Functional study of mRNA modifying protein RnaseR
2’O methylation (2’Ome) is identified as a new messenger modification with unknown biological functions. Mycoplasma genitalium RNaseR stops the exonuclease activity at four nucleotides before the 2’O methylation sites in messenger RNA, which provides us an adventitious opportunity to map this new modification. In this project, we are interested in determining the crystal structure of RNaseR, which will increase our understanding of RnaseR at the molecular level.
Slot 2: Coregulation of messenger RNA and transfer RNA through RNA modifications
Reprogramming of transfer RNA and messenger RNA constantly occurs during the developmental process. However, it remains elusive how these two RNA species are coordinated to balance the codon and anti-codon availability. We identified Mettl1, a N7-methylguanosine methyltransferase is critical in coordinating tRNA and mRNA availability. In this project, we will characterize the substrate selection and the cellular impact of Mettl1-mediated RNA methylation by using a series of biochemistry and cellular biological approaches.
Slot 3: Transcriptome mapping of new mRNA modifications by LC-MS/MS and high-throughput sequencing
Our LC-MS/MS result revealed two new RNA modifications existing in messenger RNA. They are 8-oxoguanine (8OxoG) and N6-threonylcarbamoyladenosine (t6A). In this project, we will determine the genome location and the abundance of these two RNA modifications by using LC-MS/MS and high-throughput sequencing.