Aging-associated long non-coding RNA boosts longevity and reduces the ribosome content of non-dividing fission yeast cells

Abstract

Genomes produce widespread long non-coding RNAs (lncRNAs) of largely unknown functions. We characterize aal1 (aging-associated lncRNA) which is induced in quiescent cells of fission yeast. Deletion of aal1 shortens the chronological lifespan of non-dividing cells, while ectopic overexpression of aal1 prolongs their lifespan, indicating that this lncRNA acts in trans. The overexpression of aal1 leads to the repression of ribosomal protein genes and inhibition of cell growth, and aal1 genetically interacts with coding genes functioning in protein translation. The aal1 RNA localizes to the cytoplasm and associates with ribosomes. Notably, aal1 deletion or overexpression is sufficient to increase or decrease the cellular ribosome content. The rpl1901 mRNA, encoding a ribosomal protein, is a binding target of aal1. The levels of rpl1901 are reduced [~]2-fold by aal1, which is critical and sufficient to extend the lifespan. Remarkably, the expression of aal1 lncRNA in Drosophila triggers an extension of fly lifespan. We propose that aal1 reduces the ribosome content by decreasing the levels of Rpl1901, thus attenuating protein translation and promoting longevity. Although the aal1 lncRNA itself is not conserved, its effect in flies raises the possibility that animals feature related mechanisms that modulate aging, based on the conserved translational machinery.