Modification of messenger RNA by 2′-O-methylation regulates gene expression in vivo

Brittany A. Elliott, Hsiang-Ting Ho, Srivathsan V. Ranganathan, Sweta Vangaveti, Olga Ilkayeva, Hala Abou Assi, Alex K. Choi, Paul F. Agris and Christopher L. Holley ()
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Brittany A. Elliott: Duke University Medical Center
Hsiang-Ting Ho: Duke University Medical Center
Srivathsan V. Ranganathan: State University of New York
Sweta Vangaveti: State University of New York
Olga Ilkayeva: Duke University
Hala Abou Assi: Duke University Medical Center
Alex K. Choi: Duke University Medical Center
Paul F. Agris: Duke University Medical Center
Christopher L. Holley: Duke University Medical Center

Nature Communications, 2019, vol. 10, issue 1, 1-9

Abstract: Abstract Epitranscriptomic modifications of mRNA are important regulators of gene expression. While internal 2′-O-methylation (Nm) has been discovered on mRNA, questions remain about its origin and function in cells and organisms. Here, we show that internal Nm modification can be guided by small nucleolar RNAs (snoRNAs), and that these Nm sites can regulate mRNA and protein expression. Specifically, two box C/D snoRNAs (SNORDs) and the 2′-O-methyltransferase fibrillarin lead to Nm modification in the protein-coding region of peroxidasin (Pxdn). The presence of Nm modification increases Pxdn mRNA expression but inhibits its translation, regulating PXDN protein expression and enzyme activity both in vitro and in vivo. Our findings support a model in which snoRNA-guided Nm modifications of mRNA can regulate physiologic gene expression by altering mRNA levels and tuning protein translation.

Date: 2019
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DOI: 10.1038/s41467-019-11375-7

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