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

Abstract

AbstractGenomes produce widespread long non-coding RNAs (lncRNAs) of largely unknown functions. We characterizeaal1(aging-associated lncRNA) which is induced in quiescent cells of fission yeast. Deletion ofaal1shortens the chronological lifespan of non-dividing cells, while ectopic overexpression ofaal1prolongs their lifespan, indicating that this lncRNA actsin trans. The overexpression ofaal1leads to the repression of ribosomal protein genes and inhibition of cell growth, andaal1genetically interacts with coding genes functioning in protein translation. Theaal1RNA localizes to the cytoplasm and associates with ribosomes. Notably,aal1deletion or overexpression is sufficient to increase or decrease the cellular ribosome content. Therpl1901mRNA, encoding a ribosomal protein, is a binding target ofaal1.The levels ofrpl1901are reduced ∼2-fold byaal1,which is critical and sufficient to extend the lifespan. Remarkably, the expression ofaal1lncRNA inDrosophilatriggers an extension of fly lifespan. We propose thataal1reduces the ribosome content by decreasing the levels of Rpl1901, thus attenuating protein translation and promoting longevity. Although theaal1lncRNA 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.