Katsura Asano, Professor
258 Chalmers Hall
Ph.D. 1994, University of Tokyo, Japan.
Area(s) of Specialization
Regulation of protein biosynthesis
Yeast genetics and biochemistry
Molecular and cell biology of insects and cancer
Our long-term goal is to understand the mechanism and control of eukaryotic translation initiation at the molecular level. Translation initiation is the rate-limiting step of protein biosynthesis and an important target for the control of gene expression. Unregulated translation initiation is an important phenotype of malignantly transformed cells. We are particularly interested in the biological effects of translational regulation by altering the choice of start codons, including non-AUG start codons.
The main player of our projects is translation initiation multifactor complex (MFC), a ~1 MDa complex made of eukaryotic initiation factors (eIF) 1, 2, 3, 5 and the initiator Met-tRNA. This is found in all the eukaryotic species examined so far including humans and yeasts. MFC allows stringent translation initiation at AUG codons and serves as the platform of complex translational regulation required for higher-ordered eukaryotic functions. We dissect MFC functions by genetics using mutations in two proteins, eIF3e/Int-6 and eIF5-mimic protein (5MP). Being located in the structural core of eIF3, eIF3e plays an important role in translational regulation, coordinating cellular proliferation and metabolism. As a molecular mimic and competitor of eIF5, 5MP inhibits MFC function, regulating initiator Met-tRNA recruitment to the ribosome and stringency of translation initiation. We use yeasts, insects, and human cells, including cancer cells, to study MFC functions in stringent translation initiation, cell differentiation, and neuronal growth regulation.
Eiji Obayashi, Rafael E. Luna, Takashi Nagata, Pilar Martin-Marcos, Hiroyuki Hiraishi, Chingakham Ranjit Singh, Jan Peter Erzberger, Fan Zhang, Haribabu Arthanari, Jacob Morris, Riccardo Pellarin, Chelsea Moore, Ian Harmon, Evangelos Papadopoulos, Hisashi Yoshida, Mahmoud L. Nasr, Satoru Unzai, Brytteny Thompson, Eric Aube, Samantha Hustak, Florian Stengel, Eddie Dagraca, Asokan Ananbandam, Philip Gao, Takeshi Urano, Alan G. Hinnebusch, Gerhard Wagner, and Katsura Asano. 2017. Molecular landscape of the ribosome pre-initiation complex during mRNA scanning: structural role for eIF3c and its control by eIF5. Cell Reports 18: 2651–2663.
Caitlin Kozel, Brytteny Thompson, Samantha Hustak, Chelsea Moore, Akio Nakashima, Chingakham Ranjit Singh, Megan Reid, Christian Cox, Evangelos Papadopoulos, Rafael E. Luna, Abbey Anderson, Hideaki Tagami, Hiroyuki Hiraishi, Emily Archer Slone, Ken-ichi Yoshino, Masayo Asano, Sarah Gillaspie, Jerome Nietfeld, Jean-Pierre Perchellet, Stefan Rothenburg, Hisao Masai, Gerhard Wagner, Alexander Beeser, Ushio Kikkawa, Sherry D. Fleming, and Katsura Asano. 2016. Overexpression of eIF5 or its protein mimic 5MP perturbs eIF2 function and induces ATF4 translation through delayed re-initiation. Nucl. Acids Res. 44, 8704-8713.
Asano, K. 2014. Why is start codon selection so precise in eukaryotes? Review. Translation 2, e28387.
Hiraishi H, Oatman J, Haller S, Blunk L, McGivern B, Morris J, Papadopoulos E, Gutierrez W., Gordon M, Bokhari W, Ikeda Y, Miles D, Fellers J, Asano M, Wagner G, Tazi L, Rothenburg S, Brown SJ, Asano K. 2014. Essential role of eIF5-mimic protein in animal development is linked to control of ATF4 expression. Nucl Acids Res 42, 10321–10330.
Luna RE, Arthanari H, Hiraishi H ,Akabayov B, Tang L, Cox C, Markus MA, Luna L, Ikeda Y, Watanabe R, Bedoya E, Yu C, Alikhan S, Wagner G, and Asano K. 2013. The interaction between eukaryotic initiation factor 1A and eIF5 retains eIF1 within scanning preinitiation complexes. Biochemistry 52, 9510-9518.
Hiraishi H., Shin B-s, Udagawa T, Nemoto N, Chowdhury W, Graham J, Cox C, Reid M, Brown SJ, Asano K. 2013. Interaction between 25S rRNA A loop and eIF5B promotes subunit joining and ensures stringent AUG selection. Mol. Cell. Biol. 33, 3540–3548.
Singh CR, Watanabe R, Chowdhury W, Hiraishi H, Murai MJ, Yamamoto Y, Miles D, Ikeda Y, Asano M, Asano K. 2012. Sequential eIF5 binding to the charged disordered segments of eIF4G and eIF2β stabilizes the 48S pre-initiation complex and promotes its shift to the initiation mode. Mol. Cell. Biol. 32, 3978-3989.