Upregulation of aal1 Long Non-Coding RNA Extends Life in Flies
Researchers here report on the discovery of a long non-coding RNA that in flies reduces the pace of creation of ribosomes, and thus the pace of protein synthesis in ribosomes, by inhibiting production of a specific ribosomal protein. The result is extended lifespan. This is intriguing, as improving ribosomal function has been shown to extend life in short-lived species, and this does not have the look of an improvement. But equally, there are signs that long-lived individuals may exhibit reduced creation of ribosomes. Protein synthesis in ribosomes is also reduced in a number of life extending interventions, such as calorie restriction and its mimetics. As for all matters of cellular biochemistry in the context of aging, the influence of ribsosomal activity is complex and the fine details matter.
Genomes produce widespread long non-coding RNAs (lncRNAs) of largely unknown functions. We characterize aal1 (ageing-associated lncRNA), which is induced in quiescent fission yeast cells. Deletion of aal1 shortens the chronological lifespan of non-dividing cells, while ectopic overexpression prolongs their lifespan, indicating that aal1 acts in trans. Overexpression of aal1 represses ribosomal-protein gene expression and inhibits cell growth, and aal1 genetically interacts with coding genes functioning in protein translation. The aal1 lncRNA localizes to the cytoplasm and associates with ribosomes. Notably, aal1 overexpression decreases the cellular ribosome content and inhibits protein translation.
The aal1 lncRNA binds to the rpl1901 mRNA, encoding a ribosomal protein. The rpl1901 levels are reduced ~2-fold by aal1, which is sufficient to extend lifespan. Remarkably, the expression of the aal1 lncRNA in Drosophila boosts fly lifespan. We propose that aal1 reduces the ribosome content by decreasing Rpl1901 levels, thus attenuating the translational capacity and promoting longevity. Although aal1 is not conserved, its effect in flies suggests that animals feature related mechanisms that modulate ageing, based on the conserved translational machinery.