Chemistry:N1-Methylguanosine
N1-Methylguanosine (also 1-Methylguanosine or m1G) is a modified nucleoside, derived from guanosine through the addition of a methyl group to the nitrogen atom at position 1 of the guanine base. This modification results in a fixed positive charge on the purine ring. It occurs in all transfer RNAs (tRNAs) that read codons starting with C except in those tRNAs that read CAN codons.[1][2]
m1G can help prevent errors in protein synthesis, and lower levels can cause significant errors, reduction of protein output, and lower cell viability. Additionally, as a RNA component, it is excreted in urine and elevated levels may be usable as an indicator of certain cancers.
Occurrence and function
The most extensively studied function of m1G is in tRNA, where it is typically found at position 37 (m1G37), immediately 3' to the anticodon. This modification is critical for maintaining translational fidelity.[3] The presence of m1G37, with its positive charge and steric bulk, helps prevent frameshift errors during protein synthesis, particularly at codons susceptible to +1 frame-shifting, by stabilizing the codon-anticodon interaction and ensuring correct alignment within the ribosome.[1] Loss of m1G37 modification can lead to significant translational errors, global reduction of protein output,[4] and reduced cell viability.[5][6] In addition to its presence in position 37, m1G is also found in position 9 of many cytosolic and mitochondrial tRNAs.[7] The presence of m1G in tRNA has also been identified as part of the epitranscriptome.[7]
Biosynthesis
Clinical significance
Modified nucleosides, generated from the catabolism of RNA, are excreted in urine.[8] Altered levels of RNA turnover and modification often occur in disease states, particularly cancer.[9] Consequently, urinary concentrations of various modified nucleosides, including m1G, have been investigated as potential non-invasive biomarkers.[9] Studies have reported elevated urinary m1G levels, along with other modified nucleosides, in patients with various malignancies, including breast cancer, lung cancer, leukemia, ovarian cancer, and renal cell carcinoma, often correlating with tumor stage or progression.[9]
See also
- Guanosine
- 7-Methylguanosine (m7G)
- RNA modification
- Epitranscriptomics
- Transfer RNA
- Methyltransferase
- Nucleoside
References
- ↑ 1.0 1.1 Björk, Glenn R.; Wikström, P. Mikael; Byström, Anders S. (1989-05-26). "Prevention of Translational Frameshifting by the Modified Nucleoside 1-Methylguanosine" (in en). Science 244 (4907): 986–989. doi:10.1126/science.2471265. ISSN 0036-8075. PMID 2471265. Bibcode: 1989Sci...244..986B. https://www.science.org/doi/10.1126/science.2471265.
- ↑ Cantara, W. A.; Crain, P. F.; Rozenski, J.; McCloskey, J. A.; Harris, K. A.; Zhang, X.; Vendeix, F. A. P.; Fabris, D. et al. (2011-01-01). "The RNA modification database, RNAMDB: 2011 update" (in en). Nucleic Acids Research 39 (Database): D195–D201. doi:10.1093/nar/gkq1028. ISSN 0305-1048. PMID 21071406.
- ↑ Björk, Glenn R.; Ericson, Johanna U.; Gustafsson, Claes E. D.; Hagervall, Tord G.; Jönsson, Yvonne H.; Wikström, P. Mikael (1987). "Transfer RNA Modification" (in en). Annual Review of Biochemistry 56: 263–285. doi:10.1146/annurev.bi.56.070187.001403. ISSN 0066-4154. PMID 3304135.
- ↑ Jin, Xiaohuan; Lv, Zhengyi; Gao, Junbao; Zhang, Rui; Zheng, Ting; Yin, Ping; Li, Dongqin; Peng, Liangcai et al. (2019-01-25). "AtTrm5a catalyses 1-methylguanosine and 1-methylinosine formation on tRNAs and is important for vegetative and reproductive growth in Arabidopsis thaliana". Nucleic Acids Research 47 (2): 883–898. doi:10.1093/nar/gky1205. ISSN 0305-1048. PMID 30508117. PMC 6344853. https://academic.oup.com/nar/article/47/2/883/5223939.
- ↑ Masuda, Isao; Yamaki, Yuka; Detroja, Rajesh; Tagore, Somnath; Moore, Henry; Maharjan, Sunita; Nakano, Yuko; Christian, Thomas et al. (2022-10-25). "tRNA methylation resolves codon usage bias at the limit of cell viability". Cell Reports 41 (4). doi:10.1016/j.celrep.2022.111539. ISSN 2211-1247. PMID 36288695.
- ↑ Li, J N; Björk, G R (November 1995). "1-Methylguanosine deficiency of tRNA influences cognate codon interaction and metabolism in Salmonella typhimurium". Journal of Bacteriology 177 (22): 6593–6600. doi:10.1128/jb.177.22.6593-6600.1995. PMID 7592438.
- ↑ 7.0 7.1 Dannfald, Arnaud; Favory, Jean-Jacques; Deragon, Jean-Marc (2021-10-15). "Variations in transfer and ribosomal RNA epitranscriptomic status can adapt eukaryote translation to changing physiological and environmental conditions". RNA Biology 18 (sup1): 4–18. doi:10.1080/15476286.2021.1931756. ISSN 1555-8584. PMID 34159889.
- ↑ Schöch, G.; Topp, H.; Held, A.; Heller-Schöch, G.; Ballauff, A.; Manz, F.; Sander, G. (September 1990). "Interrelation between whole-body turnover rates of RNA and protein". European Journal of Clinical Nutrition 44 (9): 647–658. ISSN 0954-3007. PMID 1702054.
- ↑ 9.0 9.1 9.2 Seidel, A.; Brunner, S.; Seidel, P.; Fritz, G. I.; Herbarth, O. (2006-06-05). "Modified nucleosides: an accurate tumour marker for clinical diagnosis of cancer, early detection and therapy control". British Journal of Cancer 94 (11): 1726–1733. doi:10.1038/sj.bjc.6603164. ISSN 0007-0920. PMID 16685264.
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