Loss of the ribosomal RNA methyltransferase NSUN5 impairs global protein synthesis and normal growth
| Autor: | Clemens, Heissenberger, Lisa, Liendl, Fabian, Nagelreiter, Yulia, Gonskikh, Guohuan, Yang, Elena M, Stelzer, Teresa L, Krammer, Lucia, Micutkova, Stefan, Vogt, David P, Kreil, Gerhard, Sekot, Emilio, Siena, Ina, Poser, Eva, Harreither, Angela, Linder, Viktoria, Ehret, Thomas H, Helbich, Regina, Grillari-Voglauer, Pidder, Jansen-Dürr, Martin, Koš, Norbert, Polacek, Johannes, Grillari, Markus, Schosserer |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Mice Knockout Nucleic Acid Enzymes Body Weight Infant Muscle Proteins Methyltransferases Cell Enlargement Embryo Mammalian Mice Inbred C57BL Mice HEK293 Cells Protein Biosynthesis 540 Chemistry Animals Humans 570 Life sciences biology Female Growth and Development Child Cells Cultured Gene Deletion Cell Proliferation HeLa Cells |
| Zdroj: | Heissenberger, Clemens; Liendl, Lisa; Nagelreiter, Fabian; Gonskikh, Yulia; Yang, Guohuan; Stelzer, Elena M.; Krammer, Teresa L.; Micutkova, Lucia; Vogt, Stefan; Kreil, David P.; Sekot, Gerhard; Siena, Emilio; Poser, Ina; Harreither, Eva; Linder, Angela; Ehret, Viktoria; Helbich, Thomas H.; Grillari-Voglauer, Regina; Jansen-Dürr, Pidder; Koš, Martin; ... (2019). Loss of the ribosomal RNA methyltransferase NSUN5 impairs global protein synthesis and normal growth. Nucleic acids research, 47(22), pp. 11807-11825. Oxford University Press 10.1093/nar/gkz1043 Nucleic Acids Research |
| Popis: | Modifications of ribosomal RNA expand the nucleotide repertoire and thereby contribute to ribosome heterogeneity and translational regulation of gene expression. One particular m5C modification of 25S ribosomal RNA, which is introduced by Rcm1p, was previously shown to modulate stress responses and lifespan in yeast and other small organisms. Here, we report that NSUN5 is the functional orthologue of Rcm1p, introducing m5C3782 into human and m5C3438 into mouse 28S ribosomal RNA. Haploinsufficiency of the NSUN5 gene in fibroblasts from William Beuren syndrome patients causes partial loss of this modification. The N-terminal domain of NSUN5 is required for targeting to nucleoli, while two evolutionary highly conserved cysteines mediate catalysis. Phenotypic consequences of NSUN5 deficiency in mammalian cells include decreased proliferation and size, which can be attributed to a reduction in total protein synthesis by altered ribosomes. Strikingly, Nsun5 knockout in mice causes decreased body weight and lean mass without alterations in food intake, as well as a trend towards reduced protein synthesis in several tissues. Together, our findings emphasize the importance of single RNA modifications for ribosome function and normal cellular and organismal physiology. |
| Databáze: | OpenAIRE |
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