The roles of N2-methylguanosine in cellular RNAs

• Applicant: Katherine Bohnsack, Ph.D.
• Subject Area: Biochemistry
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 560188066

Modified nucleosides in cellular RNAs are critical for gene expression and endow an important layer of dynamic regulation. A plethora of non-canonical nucleosides have been detected in cellular RNAs (the epitranscriptome) and several RNA modifications have been mapped across the transcriptome. Within coding RNAs (mRNAs) as well as non-coding RNAs, such as a transfer (t)RNAs and small nuclear (sn)RNAs, modified nucleosides contribute to RNA folding as well as modulating RNA–RNA and RNA–protein interactions. Due to the important roles that RNA modifications play in gene expression and its regulation, perturbation of the epitranscriptome is often associated with disease. Identification of the enzymes responsible for modifying particular RNA nucleosides is essential for understanding how these marks are introduced as well as what consequences they have on RNA functions and cellular physiology. Methylation is the most common type of RNA modification and the formation of N2-methylguanosine (m2G) has recently come into focus with the identification of three related methyltransferase responsible for installing this type of modification in human RNAs. While m2G has long been known to be present in human tRNAs and the U6 snRNA, new evidence suggests a more wide-spread existence of m2G throughout the transcriptome. In this project, we will combine classical molecular biology and biochemistry approaches with innovative RNA modification detection approaches towards i) eluciating the molecular basis of installation of m2G modifications in cellular RNAs and ii) determining the roles that these methylations play in RNA metabolism. This project will therefore extend fundamental knowledge on the biogenesis of different components of the gene expression machinery and reveal the functions of modified nucleosides within the RNAs involved.

• DFG Programme: Research Grants