Yuru Wang
Assistant Professor of Medicinal Chemistry
Epitranscriptomics, RNA Modifications, RNA Editing, Pseudouridine, Inosine, Protein Evolution, Biomedicine, RNA Therapeutics
Molecular Biology Program
Biological Chemistry Program
Education
B.S. Nankai University
Ph.D. University of California, Davis
Research
Eukaryotic RNAs undergo a complex process of modification, which is indispensable for the normal function of cells. These RNA modifications encompass a wide array of chemical alterations, including methylation (e.g., N6-methyladenosine, m7G, m1A, Nm), deamination (e.g., I), acetylation (e.g., ac4C), and isomerization (e.g., Pseudouridine). Leveraging their unique chemical attributes, these modifications have the potential to regulate RNA properties such as stability, transcription, and translation, which exerts a profound influence on various cellular processes, including immune responses, phase seperation, and embryonic cell division. Aberrations in modification distribution or extent have been associated with cellular malfunctions and human diseases.
Despite advancements in technologies that enable mapping and analysis of certain modifications, our understanding of their dynamics and functions remains in its infancy. Moreover, given RNA's pivotal role in cellular processes, breakthroughs in biotechnologies centered on RNA and its modifications have sparked a revolution in both fundamental research and clinical applications.
The Wang lab is deeply intrigued by the mechanisms underlying the regulatory installation, recognition and functions of specific modifications, such as pseudouridine and inosine. To unravel these mysteries, we are committed to pioneering novel cell-based assays and studying the modifications in specific biological contexts, such as during the innate immune response and in disease status. Armed with a deeper understanding of the regulatory mechanisms governing modification installation and their functional outcomes, we aspire to achieve precise, site-directed modulation of specific modifications at chosen locations, thereby fine-tuning properties of critical disease-related RNAs. Furthermore, our research endeavors extend to the development of cutting-edge molecular devices designed for the exploration of spatial and temporal dynamics of essential modifications within living cells. This will add to the toolkit to facilitate unprecedent studies of RNA modifications.
Trainees at the Wang lab will thrive in an interdisciplinary environment that encompasses fields such as biochemistry, RNA biology, mass spectrometry, protein engineering and genetics. Our ultimate objectives are to advance the development of innovative RNA therapeutics and uncover novel drug targets to combat human diseases.
References
- Wang, Y., Zhang, Z., Sepich, C., Zhang, L., Xiao, Y., and He, C. (2020) LEAD-m6A-seq for locus-specific detection of N6-methyladenosine and quantification of differential methylation. Angew. Chem. Int. Ed., 60 (2), 873-880. Featured as VIP (very important paper).
- Wang, Y., Katanski, C.D., Watkins, C., Pan, J.N., Dai, Q., Jiang, Z., and Pan, T. (2020) A high throughput screening method for evolving a demethylase enzyme with new functionalities. Nucleic Acids Res. DOI: 10.1093/nar/gkaa1213
- Wang, Y., Chung, D., Monteleone, L.R., Li, J., Chiang, Y., Toney, M., and Beal, P.A. (2019) RNA Binding Candidates for Human ADAR3 from Substrates of a Gain of Function Mutant Expressed in Neuronal Cells. Nucleic Acids Res., 47(20), 10801-10814.
- Wang, Y. Park, S. and Beal, P. A. (2018) Selective recognition of RNA substrates by ADAR deaminase domains. Biochemistry, 57(10),1640-1651
- Wang, Y., Zheng Y. and Beal, P.A. (2017) Adenosine Deaminases that Act on RNA (ADARs). The Enzymes, 41, 215-268. (invited book chapter)
- Wang, Y. and Beal, P.A. (2016) Probing RNA recognition by human ADAR2 using a high-throughput mutagenesis method. Nucleic Acids Res., 44(20), 9872-9880.
- Wang, Y., Havel, J. and Beal, P.A. (2015) A phenotypic screen for functional mutants of human adenosine deaminase acting on RNA 1. ACS Chem. Biol., 10, 2512-2519.
- Dai, Q.; Zhang, L.; Sun, H.; Pajdzik, K.; Yang, L.; Ye, C.; Ju, C.; Liu, S.; Wang, Y.; Zheng, Z.; Zhang, L.; Harada, B.; Irkliyenko, I.; Zhang, W.; Pan, T.; and He, C. (2023) Quantitative sequencing uncovers abundant pseudouridines in mammalian mRNA at base resolution. Nat. Biotech., 41, 344–354