Medical Sciences Group／Intra-University Cooperative LaboratoriesInada Laboratory
(Division of RNA and Gene Regulation, IMS)
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Professor INADA Toshifumi
Elucidate the mechanism that guarantees the accuracy of gene expression
Accurate gene expression is the basis of all life phenomena, and the production of aberrant proteins is considered to be the root cause of disruption of protein homeostasis. Abnormal proteins are produced by various factors after translation, including changes in conformation, but it has become clear that they are also produced by abnormal mRNA, inaccurate translation, and abnormal ribosomes. We have discovered RQC (Ribosome-associated quality control), which recognizes abnormal translation elongation and degrades nascent polypeptide chains in the process of synthesis, and have elucidated the fate determination mechanism by specific ubiquitination of the ribosome. In addition, he has elucidated the function of ubiquitin at specific sites of ribosomal proteins by E3 ubiquitin ligation for NRD (Non-functional rRNA Decay), a quality control mechanism that degrades functionally defective ribosomes. These molecular mechanisms of translation quality control, which suppress the production of abnormal proteins and maintain protein homeostasis, are expected to provide the molecular basis for drug discovery related to diseases caused by various abnormal protein accumulations (neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease) and aging.
- Research
keywords - Translation quality control, RNA regulation, Ribosome, Ubiquitination, Proteostasis, Proteasome, Ribosomopathys
To decipher the mechanism to ensure the fidelity of protein synthesis
The field of biology has expanded from the traditional approaches of focusing on specific organisms and phenomena to utilizing data science approaches in the pursuit of obtaining a comprehensive understanding of life. Under this context, our laboratory employs interdisciplinary approaches, including but not limited to: bioinformatics, laboratory experiments, mathematics, and field samplings to study evolution and ecology of diverse life forms, and to develop novel biotechnological methods.
Topics and Questions
(1) Molecular mechanism of quality control RQC that guarantees translation accuracy:How are translation anomalies perceived, and how are anomalous proteins decomposed and eliminated? (2) Physiological significance of translation quality control in nerve cells: What kind of abnormal translation occurs in nerve cells and is recognized and eliminated by quality control? (3) Ribosome abnormalities and diseases: How are abnormal ribosomes recognized and eliminated?How do diseases caused by ribosome abnormalities develop? (4) Aging and translation accuracy: What is the substance of protein homeostasis due to aging?
The related research fields and research areas are as follows.
[Genetics / Biochemistry] Translation quality control / RNA expression control
[Cell biology/neuroscience] Neuronal cell death and disease onset mechanism due to disruption of protein homeostasis
[Structural biology] Single particle analysis of ribosomes and quality control factors using cryo-electron microscopy
References/papers
- Publications in the last several years contributed by graduate students
- Udagawa, Seki, Okuyama et al., Cell Rep. 2021; Mizuno et al., NAR 2021; Buschauer, Matsuo et al., Science 2020; Matsuki and Matsuo et al., Sci Rep 2020; Matsuki and Matsuo et al., BBRC 2020; Matsuo et al., NSMB 2020; Hashimoto et al., Sci. Rep. 2020; Hashimoto et al., FEBS Letters 2019; Sugiyama, Li, Kato et al., Cell Rep. 2019; Ikeuchi et al., EMBO J. 2019
