Scientists from the Valrose Institute of Biology in Nice, France, by combining high-resolution imaging and functional approaches, discovered that RNAs selectively condense in the aging brain and were able to identify the underlying mechanisms .
The condensation of RNAs being associated with the repression of their translation, these results, published in the journal Nature Communications, open up new perspectives in the field of the biology of aging, underline the researchers.
Cytoplasmic ribonucleoprotein condensates (RNPs), rich in mRNA and regulatory proteins, are present in various cell types and are associated with regulatory or storage functions. In recent years, a clear link has been established between the accumulation of aberrant RNP aggregates and the progression of age-related neurodegenerative diseases, it is observed, noting that the impact of physiological aging on neuronal RNP aggregates n however, has never been explored outside of pathological contexts.
Scientists also found that constituents of RNP condensates gradually condense during aging to form large but dynamic granules in Drosophila brain. Using functional approaches, they show that this increased condensation is caused by an increase in the levels of the protein helicase Me31B/DDX6 during aging, and that it requires the activity of a kinase, PKA.
Remarkably, they note, mRNA species recruited into RNP condensates during aging experience repression of their translation into proteins, indicating that selective condensation of mRNAs and translational repressors could contribute to the observed gene expression changes. during physiological aging. Moreover, the mechanisms highlighted could be generalizable because the Me31B/DDX6 helicase and the PKA kinase are evolutionarily highly conserved.
These results confirm the conclusions of a previous German study which also highlighted changes in the properties of DDX6 protein-rich condensates during neuronal maturation, reinforcing the idea that this is a fundamental conserved process. during evolution.