Non-coding RNA

Lost on translation

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.

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Sheppard, T. Lost on translation. Nat Chem Biol 10, 408 (2014). https://doi.org/10.1038/nchembio.1538

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