定量生命科学研究所セミナー(11月5日)
日 時:2024年11月5日(火) 11:00-12:00
場 所: 生命科学総合研究棟 B棟301
講 師:Tomohisa Toda, Ph.D.
Professor Friedrich-Alexander Universität Erlangen-Nürnberg/Max-Planck-Zentrum für Physik und Medizin
演 題:Exploration of long-lived cellular constituents for neural plasticity and brain aging
要 旨:
Ageing is one of the most critical risk factors for neurological and psychiatric disorders. However, the biological links between physiological ageing and pathological development are
still largely unknown. Therefore, a solid understanding of the biology of brain ageing will thus be a key to developing the means to treat these diseases. Because neurons and adult neural progenitor cells in the brain are mostly generated during development with limited capacity of replacement, they must maintain their identity and function throughout life.
We recently found that a cell type-specific nuclear architecture, organized by nucleoporins and nuclear lamins, regulates the maintenance of neural identity. Strikingly, some of
nucleoporins and lamins are the most long-lived proteins in the brain and are known to be damaged during ageing, but their functional contribution in brain function and ageing remains largely elusive. In this line, we have investigated the role of nucleoporin-dependent epigenetic regulation in neurons, and found that Nup153, one of nucleoporins, balances neuronal responsiveness by regulating neural plasticity-related gene expression, which is a fundamental process for maintaining neural plasticity.
In contrast to nuclear structural proteins, the lifespan of nuclear RNAs, which are also critical for epigenetic regulation, has not been determined in mammalian tissues. We have identified RNAs that do not turnover for at least 2 years in the mouse brain. These long-lived RNAs (LLRNAs) were retained in nuclei in a neural cell type–specific manner. LL-RNAs in quiescent neural stem cells were enriched for non-coding RNAs including major satellite RNAs. Perturbation experiments revealed that major satellite RNAs are required for heterochromatin maintenance and for the reactivation of quiescent neural stem cells, suggesting their functional significance for the maintenance of somatic stem cell function.
Thus, our findings suggest that the lifespan and function of brain cells may depend on the longevity of cellular constituents, including long-lived proteins for epigenetic regulation, and the extreme stability of nuclear RNA for the functional organization of chromatin.
幹 事︓RNP生命工学研究分野
主 催︓東京大学定量生命科学研究所
後 援:公益財団法人応用微生物学・分子細胞生物学研究奨励会