Mol. Cell 54, 147–155 (2014)

In most eukaryotes, small noncoding RNAs (ncRNAs) are known to regulate gene expression at the translational level by pairing with ribosome-bound mRNAs. Yet because Saccharomyces cerevisiae lacks RNA interference pathways that are necessary to generate miRNAs, these regulatory pathways do not operate in yeast. A new study by Pircher et al. shows that yeast have an alternative mechanism for RNA-mediated translational control by identifying a small ncRNA that regulates ribosomal activity in response to stress. Building on their prior work that identified a class of small ribosome-associated ncRNAs in S. cerevisiae, the authors focused on an abundant 18-nucleotide ncRNA fragment of the Trm10 transcript (Trm-ncRNA). Trm10 knockout strains grow more slowly under hyperosmotic stress conditions, an effect that was independent of the Trm10-encoded methyltransferase protein but dependent on the presence of Trm-ncRNA. Genetic and polysome profiling experiments showed that Trm-ncRNA was stably expressed and associated with the 60S subunit of yeast ribosomes in cells. In response to hyperosmotic stress, Trm-ncRNA was redistributed to polysomes, where it blocked translation and decreased metabolic activity, permitting yeast to adapt to altered environmental conditions. Though it remains unknown how the 18-nucleotide fragment is generated from mRNA and where Trm-ncRNA acts on the ribosome, the study outlines a new mechanism for ncRNA regulation of translational activity by direct binding of the ribosome.