RNA lies at the heart of gene regulation in all biological systems, from viruses to humans. We believe that RNA research holds the key to understanding the fundamental principles underlying complex biological systems and will pave the way for engineering cell fates. Our work focuses on identifying regulatory RNAs and their associated factors and dissecting their molecular mechanisms through combination of sequencing, biochemistry, structural biology, and proteomics approaches. We also explore their functions in diverse biological contexts, including stem cells, cancer, viruses, and RNA-based therapies.
mRNA Modification and Stability: The Tail Leading the Way
RNA tailing plays a critical role in the control of RNA function and stability. We previously discovered that microRNAs are uridylated or adenylated at the 3' end and that these 3' tails regulate their biogenesis and stability. More recently, we developed a technique called TAIL-seq that allows us to investigate the status of mRNA tails at genome-scale, and discovered noncanonical types of mRNA tails, including uridylation and mixed tailing, and investigated their functions and regulatory mechanisms. We are currently focusing on mixed tailing, which is a critical mechanism for RNA stabilization in humans with a strong implication in mRNA therapeutics.
Viral Regulatory RNAs: Lessons from Viruses
For successful infections, viruses must manipulate RNA regulatory systems. In our lab, we are identifying viral RNAs with potent regulatory activities through high-throughput sequencing-based screens using thousands of viral genomes. We have discovered numerous viral elements that control translation and mRNA stability. By dissecting their action mechanisms, we hope to uncover novel regulatory pathways. Moreover, these viral RNAs offer us a unique opportunity to develop RNA therapeutics.
Regulation of Exogenous RNAs: Friend or Foe?
When exogenous RNAs, such as viral RNAs and therapeutic mRNAs, enter cells, they interact with the cellular machinery and host cellular defense systems. Understanding how these RNAs navigate these challenges is critical for their survival and translation. Currently, we are investigating the regulatory pathways governing exogenous RNAs. This study will advance our knowledge of cellular defense mechanisms against foreign RNAs and contribute to the improvement of mRNA technologies.
microRNAs: Tiny Regulators with Big Roles
microRNAs are small noncoding RNAs involved in virtually all aspects of animal development and diseases including cell differentiation, cell proliferation, cell death, energy metabolism, and antiviral defense. Tight control of microRNA is critical for normal functioning of cells, and the dysregulation of microRNAs is often responsible for human diseases. Our lab has contributed to the understanding of microRNA biogenesis by identifying key factors in the pathway, including DROSHA, DGCR8, LIN28, and TUTases and solving the first structures of Drosha and human Dicer in the past state. We are studying the mechanism of these core factors at the atomic level.
Join the RNA world!
We welcome postdoc/student applications from all around the world and all areas of biology, chemistry, and computational sciences. For more information and inquiries, please email us atlabs@narrykim.com
