Ageing-associated long non-coding RNA extends lifespan and reduces translation in non-dividing cells [aal1_ChIRP-RNAseq]
Genomes pervasively produce long non-coding RNAs (lncRNAs) of largely unknown functions. Some of these lncRNAs have been implicated in roles related to ageing and associated diseases. Here we characterize aal1 (ageing-associated lncRNA 1) which is induced in non-dividing, ageing cells of fission yeast. Deletion of aal1 shortens the chronological lifespan of non-dividing cells, while ectopic overexpression of aal1 from a plasmid prolongs their lifespan, indicating that this lncRNA acts in trans. We find that aal1 genetically interacts with coding genes functioning in processes related to protein translation, and aal1 overexpression leads to repression of ribosomal protein genes and inhibition of cell growth. 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, respectively. We identify the mRNA rpl1901, encoding a ribosomal protein, as a binding target of aal1. The expression of rpl1901 is moderately repressed by aal1, and such moderate repression is critical and sufficient to extend the chronological lifespan. Remarkably, expression of the yeast aal1 lncRNA in the fly gut triggers a significant extension of the lifespan in flies. Based on these findings, we propose that the aal1 RNA can reduce the ribosome content by decreasing the levels of the Rpl1901 ribosomal protein, thus attenuating protein translation and promoting longevity. Although the aal1 lncRNA itself is not conserved, its effects in the fly raise the possibility that other organisms feature related mechanisms involving conserved ribosome-associated processes to control ageing. Overall design: To determine aal1 interacting mRNAs/RNAs we used biotinylated antisense aal1 probes to pull down aal1 and associated RNAs. Wildtype cells (wt), cells ectopically overexpressing aal1 in a plasmid (aal1OE) and aal1 deleted cells with CRISPR-Cas9 (aal1D) were grown in minimal medium (EMMG) until Day 6 after entering stationary phase before harvesting.