N6-adenosine methylation of ribosomal RNA affects lipid oxidation and stress resistance.

Liberman, Noa; O'Brown, Zach K; Earl, Andrew Scott; Boulias, Konstantinos; Gerashchenko, Maxim V; Wang, Simon Yuan; Fritsche, Colette; Fady, Paul-Enguerrand et al. · Sci Adv · 2020

basic_science · Level V

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Abstract

During stress, global translation is reduced, but specific transcripts are actively translated. How stress-responsive mRNAs are selectively translated is unknown. We show that METL-5 methylates adenosine 1717 on 18<i>S</i> ribosomal RNA in <i>C. elegans</i>, enhancing selective ribosomal binding and translation of specific mRNAs. One of these mRNAs, CYP-29A3, oxidizes the omega-3 polyunsaturated fatty acid eicosapentaenoic acid to eicosanoids, key stress signaling molecules. While <i>metl-5-</i>deficient animals grow normally under homeostatic conditions, they are resistant to a variety of stresses. <i>metl-5</i> mutant worms also show reduced bioactive lipid eicosanoids and dietary supplementation of eicosanoid products of CYP-29A3 restores stress sensitivity of <i>metl-5</i> mutant worms. Thus, methylation of a specific residue of 18<i>S</i> rRNA by METL-5 selectively enhances translation of <i>cyp-29A3</i> to increase production of eicosanoids, and blocking this pathway increases stress resistance. This study suggests that ribosome methylation can facilitate selective translation, providing another layer of regulation of the stress response.