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Publication : Modification of messenger RNA by 2'-O-methylation regulates gene expression in vivo.

First Author  Elliott BA Year  2019
Journal  Nat Commun Volume  10
Issue  1 Pages  3401
PubMed ID  31363086 Mgi Jnum  J:279411
Mgi Id  MGI:6362372 Doi  10.1038/s41467-019-11375-7
Citation  Elliott BA, et al. (2019) Modification of messenger RNA by 2'-O-methylation regulates gene expression in vivo. Nat Commun 10(1):3401
abstractText  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.
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