September 4, 2024
Niigata University
Keio University
Associate Professor Masato Yano of the Department of Neuroanatomy, Niigata University Graduate School of Medical and Dental Sciences; Project Lecturer Kayoko Yano of the Keio Frontier Research & Education Collaborative Square (K-FRECS) [K-FRECS at Tonomachi] (at the time of the research: Project Assistant Professor, Department of Neuroanatomy, Niigata University Graduate School of Medical and Dental Sciences); and Professor and Director Hideyuki Okano of the Keio University Regenerative Medicine Research Center (KRM), in a joint research project with Takeda Pharmaceutical Company Limited and the Brain Research Institute, Niigata University, have identified Quaking5 (Qki5) as the sole RNA-binding protein (RBP) specifically expressed in spinal motor neurons. Furthermore, they have revealed the existence of a molecular mechanism by which Qki5, through RNA regulation, controls the acquisition of molecular characteristics and cellular functions of motor neurons, and acts protectively against stress.
To date, various RNA-binding proteins have been identified as causative or pathogenic molecules in motor neuron diseases. However, the fundamental question of why motor neurons selectively degenerate and are lost remains unanswered, and a curative treatment has yet to be established. In this study, the research team discovered that among the many neurons in the spinal cord, Qki5 is specifically expressed and functions in motor neurons. They also found that Qki5 performs motor neuron-specific alternative splicing regulation and plays a protective role for motor neurons by acting inhibitorily on the stress response molecular mechanism. By revealing a new molecular pathway for the maintenance of motor neurons through RNA regulation, these findings are expected to contribute to the future elucidation of motor neuron cellular functions, the pathophysiology of motor neuron diseases, and the development of new therapeutic methods, including drug discovery.
These research findings were published in the online edition of the international academic journal "Proceedings of the National Academy of Sciences of the United States of America [PNAS]," issued by the National Academy of Sciences (NAS) of the United States, on September 3, 2024.
Please see below for the full press release.