Kotaro Nakanishi received his B.S. degree from Tokyo University of Science in 2000, where he was involved in the research of the allosteric mechanism of lactate dehydrogenase. He received his M.S. degree from the University of Tokyo in 2003, where he studied the recognition mechanism of arginine tRNA-specific ribonuclease, colicin D. After working in industry, Kotaro returned to academic life, and obtained his D.Sc. in 2007 from Tokyo Institute of Technology, where he used X-ray crystallography and biochemistry to study aminoacyl-tRNA synthetase and tRNA modification enzyme with Osamu Nureki. In 2008, he joined the laboratory of Dinshaw Patel in the Memorial Sloan-Kettering Cancer Center. His work there resulted in the determination of the crystal structures of Argonaute and Dicer. He was awarded Japan Society for the Promotion of Science (JSPS) for Young Scientist, JSPS for Research Abroad, and Human Frontier Science Program for Long-term Fellow. In recognition of his works, Kotaro received the RNA Society/Scaringe Award in 2012 and the Young Scientists’ Prize of the Commendation for Science and Technology by the Japanese Minister of Education, Culture, Sports, Science and Technology in 2013. He joined the Department of Chemistry & Biochemistry of Ohio State University in August of 2013.
We study the structure of macromolecules in order to understand their mechanisms of recognition.
We are able to recognize others through our five senses, sight, hearing, taste, smell and touch. Although the senses are sophisticated systems to understand objects, they sometimes lead us to misunderstandings. For example, we see a friend walking in front of us and say, “Hi John!” But then we realize it is actually someone else.
How about macromolecules in our body? Needless to say, they have neither eyes, ears, mouth, nor nose. But they behave as if they have a sense of touch to distinguish the right partner from others. Touch itself seems to be a primitive but robust system to avoid such above-mentioned miscommunications because macromolecules fully exploit their own structure designed for the specific shape of the substrate, inhibitor, other subunit, binding partner, etc. Basically unless the object snugly fits, macromolecules don’t acknowledge that it is the proper one. They communicate with each other through their unique structures. Through the use of X-ray crystallography we can gain an understanding of how these structures determine events at the atomic resolution.
Our research interest focuses on elucidating the mechanism of microRNA (miRNA)-mediated gene regulations underlying cell type determination. miRNA genes are transcribed mainly by RNA polymerase II into primary miRNAs. They are processed by microprocessor into precursor miRNAs. After transport to the cytoplasm, Dicer crops the loop of the precursor RNAs. The resultant miRNA duplexes are loaded into Argonaute protein, and subsequently one of the strands is discarded. Accordingly, the remaining single-stranded RNA called guide strand together with Argonaute forms the ribonucleoprotein complex referred to as the RNA-induced silencing complex, RISC. miRNAs recruit the RISC to the target mRNAs based on their sequence complementarity, while AGO interacts with several components required for mRNA degradation. As a result, miRNAs repress translation of mRNAs containing a partially or fully complementary sequence.
We know what events happen in this miRNA biogenesis. However, little is known about how each event happens. Our long-term goal is to take crystallographic snapshots of every step such that we understand the molecular basis at the atomic resolution.
Another interest is a completely different subject but still relevant to our research: developing a new tag capable of increasing the solubility of the subject proteins and of facilitating crystal packing.
The Nakanishi group is looking for enthusiastic and motivated graduate and undergraduate students interested in X-ray crystallography and designing a novel tag. Inquiries about possible positions in the group are welcomed.
Our group is also opening position(s) for postdoctoral fellows. Highly motivated candidates with less than 5 years of postdoctoral experience are encouraged to apply. Please send three letters along with CV by email with the title of “application for postdoc position”.
* These authors contributed equally to the works.
Nakanishi, K.*, Ascano, M.*, Gogakos, T., Ishibe-Murakami, S., Serganov, A.A., Briskin, D., Morozov, P., Tuschl, T., & Patel D.J. (2013) Eukaryote-Specific Insertion Elements Control Human ARGONAUTE Slicer Activity. Cell Rep. 3, 1893-1900.
Shen, J., Xia, W., Khotskaya, Y.B., Huo, L., Nakanishi, K., Lim, S.O., Du, Y., Wang, Y., Chang, W.C., Chen, C.H., Hsu, J.L., Lam, Y.C., James, B.P., Liu, C.G., Liu, X., Patel, D.J., & Hung, MC. (2013) EGFR Modulates miRNA Maturation in Response to Hypoxia through Phosphorylation of Ago2. Nature 497, 383-387.
Nakanishi, K.*, Weinberg, D.E.*, Bartel, D.P., & Patel, D.J. (2012) Structure of yeast Argonaute with guide RNA. Nature 486, 368-374.
Weinberg, D.E.*, Nakanishi, K.*, Patel, D.J., & Bartel, D.P. (2011) The inside-out mechanism of Dicers from budding yeasts. Cell 146, 262-276.
Nakanishi, K., Bonnefond, L., Kimura, S., Suzuki, T., Ishitani, R., & Nureki, O. (2009) Structural basis for translational fidelity ensured by transfer RNA lysidine synthetase. Nature 461, 1144-1148.
Nakanishi, K., Ogiso, Y., Nakama, T., Fukai, S., & Nureki, O. (2005) Structural basis for anticodon recognition by methionyl-tRNA synthetase. Nat. Struct. Mol. Biol. 12, 931-932.
Nakanishi, K., Fukai, S., Ikeuchi, Y., Soma, A., Sekine, Y., Suzuki, T., & Nureki, O. (2005) Structural basis for lysidine formation by ATP pyrophosphatase accompanied by a lysine-specific loop and a tRNA-recognition domain. Proc. Natl. Acad. Sci. U. S. A. 24, 7487-7492.
Nakanishi, K., & Nureki, O. (2005) Recent progress of structural biology of tRNA processing and modification. Mol. Cells. 19, 157-166.
Yajima, S., Nakanishi, K., Takahashi, K., Ogawa, T., Hidaka, M., Kezuka, Y., Nonaka, T., Ohsawa, K., & Masaki, H. (2004) Relation between tRNase activity and the structure of colicin D according to X-ray crystallography. Biochem. Biophys. Res. Commun. 24, 966-973.