Certain RNA molecules in the nerve cells in the brain last a lifetime

RNA is commonly thought of as a short-lived mediator of genetic information. Mammalian neurons’ nuclei contain genomic DNA that may be as old as the organism. The lifespan of nuclear RNAs—essential for appropriate chromatin architecture and transcription regulation—has not been established in adult tissues.

Neuroscientists from Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) identified and characterized nuclear RNAs that do not age. They found that specific RNA molecules in the nerve cells in the brain last a lifetime without being renewed.

Through this study, scientists hope to properly understand the complex aging process of the brain and gain a better understanding of related degenerative diseases.

Prof. Dr. Tomohisa Toda, Professor of Neural Epigenomics at FAU and the Max Planck Center for Physics and Medicine in Erlangen, said, “Aging neurons are an important risk factor for neurodegenerative illnesses such as Alzheimer’s. A basic understanding of the aging process and which key components are involved in maintaining cell function is crucial for effective treatment concepts:”

The Toda working group has now identified a critical aspect of brain aging in a collaborative study with neuroscientists from Dresden, La Jolla (USA), and Klosterneuburg (Austria). The scientists showed for the first time that specific types of ribonucleic acid (RNA) that protect genetic material exist for as long as the neurons themselves.

Toda explains, “This is surprising, as unlike DNA, which as a rule never changes, most RNA molecules are extremely short-lived and are constantly being exchanged.”

The Toda group collaborated with the cell biologist team of Prof. Dr. Martin Hetzer of the Institute of Science and Technology Austria (ISTA) to ascertain the lifespan of the RNA molecules.

Tomohisa Toda, who has unique expertise in epigenetics and neurobiology and was awarded an ERC Consolidator Grant for his research in 2023, said, “We succeeded in marking the RNAs with fluorescent molecules and tracking their lifespan in mouse brain cells. We were even able to identify the marked long-lived RNAs in two-year-old animals, not just in their neurons but also in somatic adult neural stem cells in the brain.”

Furthermore, the scientists found that long-lived RNAs, or LL-RNA for short, are often found in the cell’s nucleus and are intimately linked to chromatin, a complex of proteins and DNA that makes up chromosomes. This suggests that LL-RNA is essential for controlling chromatin. To verify this theory, the group used adult brain stem cell models in an in vitro experiment, lowering the LL-RNA concentration. This had the effect of significantly impairing chromatin integrity.

Tomohisa Toda said, “We are convinced that LL-RNAs play an important role in the long-term regulation of genome stability and, therefore, in the life-long conservation of nerve cells. Future research projects should give a deeper insight into the biophysical mechanisms behind the long-term conservation of LL-RNAs. We want to learn more about their biological function in chromatin regulation and how aging affects all these mechanisms.”

Journal Reference:

1. Sara Zocher, Asako Mcclokey, Anne Karasinsky et al. Lifelong persistence of nuclear RNAs in the mouse brain. Science. DOI: 10.1126/science.adf3481