A photo of Tomohisa Toda, a neuroscientist at the University of Erlangen-Nuremberg. He is in his laboratory, seated in front of a microscope.
In his lab, neuroscientist Tomohisa Toda studies how neural cells work for years without replacement and explores the effects of aging in the development of neurological diseases.
Tomohisa Toda

Scientists traditionally considered RNA to have a fast turnover inside cells. Although this view became dominant, evidence from amphibians and plants suggested otherwise.1,2 In a new study, University of Erlangen-Nuremberg neuroscientist Tomohisa Toda and his colleagues identified long-lived nuclear RNAs in the mouse brain, with a subset of these molecules likely contributing to the maintenance of chromatin integrity.3 These findings, published in Science, uncover a previously unknown temporal aspect of RNA metabolism in mammalian neurons.

“The idea that we have these very long-lasting structural RNAs is surprising and exciting,” said Mitchell Guttman, a molecular biologist at the California Institute of Technology who was not involved in the work.

The researchers labeled newly synthesized RNAs with fluorescent molecules and tracked them as the brains of newborn mice developed. Brain cells, such as hippocampal neurons and adult mouse neural stem cells, retained these RNAs for up to two years. 

When the team conducted RNA sequencing in quiescent neural progenitor cells (quiNPC), they discovered that these long-lived molecules belonged to different types of RNA, including satellite RNAs (satRNAs). Additional PCR experiments revealed that major satRNAs, which contribute to heterochromatin structural stability, were enriched.4 Knocking down these major satRNAs using clustered regularly interspaced short palindromic repeats interference induced chromatin damage in quiNPC. “These long-lived RNAs contained in the major satRNAs seem to be important for keeping the stem cell functioning for the long-term,” said Toda.

Since the researchers could not specifically deplete the long-lived major satRNAs from the cells, it is still unclear how much these molecules contributed to genome stability, noted Guttman. “I can imagine reasons why you would want structural heterochromatin RNAs to be more stable and, therefore, why these long-lived fractions might matter,” he said. “But that still needs to be tested.”   

  1. Ford PJ, et al. Dev Biol. 1977;57(2):417-426.
  2. Dure L, Waters L. Science. 1965;147(3656):410-412. 
  3. Zocher S, et al. Science. 2024;384(6691):53-59.
  4. Velazquez Camacho O, et al. Elife. 2017;6:e25293.