N1-Methylguanosine

Last updated
N1-Methylguanosine
1-Methylguanosine.svg
Chemical structure of 1-methylguanosine
Names
IUPAC name
2-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1-methylpurin-6-one
Other names
  • m1G
  • 1-Methylguanosine
  • 1-methyl-guanosine
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
KEGG
PubChem CID
  • InChI=1S/C11H15N5O5/c1-15-9(20)5-8(14-11(15)12)16(3-13-5)10-7(19)6(18)4(2-17)21-10/h3-4,6-7,10,17-19H,2H2,1H3,(H2,12,14)/t4-,6-,7-,10-/m1/s1
    Key: UTAIYTHAJQNQDW-KQYNXXCUSA-N
  • CN1C(=O)C2=C(N=C1N)N(C=N2)[C@H]3[C@@H]([C@@H]([C@H](O3)CO)O)O
Properties
C11H15N5O5
Molar mass 297.27 g/mol
AppearanceWhite crystalline solid
Soluble in water
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

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]

Contents

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

The methylation of guanosine at the N-1 position is catalyzed by specific RNA methyltransferase enzymes using S-adenosyl methionine (SAM) as the methyl donor. In bacteria, the enzyme responsible for m1G37 formation is TrmD (tRNA (guanine37-N1)-methyltransferase). [1] TrmD is essential for the viability of many bacteria, making it an attractive target for the development of new antibiotics. In archaea and eukaryotes, the orthologous enzyme is Trm5. [7] Despite catalyzing the same reaction, Trm5 enzymes differ significantly in structure and mechanism from bacterial TrmD.[ citation needed ]

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] [10] Consequently, urinary concentrations of various modified nucleosides, including m1G, have been investigated as potential non-invasive biomarkers. [11] 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. [11]

See also

References

  1. 1 2 3 Björk, Glenn R.; Wikström, P. Mikael; Byström, Anders S. (1989-05-26). "Prevention of Translational Frameshifting by the Modified Nucleoside 1-Methylguanosine". Science. 244 (4907): 986–989. Bibcode:1989Sci...244..986B. doi:10.1126/science.2471265. ISSN   0036-8075. PMID   2471265.
  2. ↑ Cantara, W. A.; Crain, P. F.; Rozenski, J.; McCloskey, J. A.; Harris, K. A.; Zhang, X.; Vendeix, F. A. P.; Fabris, D.; Agris, P. F. (2011-01-01). "The RNA modification database, RNAMDB: 2011 update". Nucleic Acids Research. 39 (Database): D195 –D201. doi:10.1093/nar/gkq1028. ISSN   0305-1048. PMC   3013656 . PMID   21071406.
  3. ↑ Björk, Glenn R.; Ericson, Johanna U.; Gustafsson, Claes E. D.; Hagervall, Tord G.; Jönsson, Yvonne H.; Wikström, P. Mikael (1987). "Transfer RNA Modification". Annual Review of Biochemistry. 56: 263–285. doi:10.1146/annurev.bi.56.070187.001403. ISSN   0066-4154. PMID   3304135.
  4. ↑ Jin, Xiaohuan; Lv, Zhengyi; Gao, Junbao; Zhang, Rui; Zheng, Ting; Yin, Ping; Li, Dongqin; Peng, Liangcai; Cao, Xintao; Qin, Yan; Persson, Staffan; Zheng, Bo; Chen, Peng (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. PMC   6344853 . PMID   30508117.
  5. ↑ Masuda, Isao; Yamaki, Yuka; Detroja, Rajesh; Tagore, Somnath; Moore, Henry; Maharjan, Sunita; Nakano, Yuko; Christian, Thomas; Matsubara, Ryuma; Lowe, Todd M.; Frenkel-Morgenstern, Milana; Hou, Ya-Ming (2022-10-25). "tRNA methylation resolves codon usage bias at the limit of cell viability". Cell Reports. 41 (4): 111539. doi:10.1016/j.celrep.2022.111539. ISSN   2211-1247. PMC   9643105 . PMID   36288695.
  6. ↑ 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. PMC   177513 . PMID   7592438.
  7. 1 2 3 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. PMC   8677040 . PMID   34159889.
  8. ↑ 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. ↑ 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. PMC   2361309 . PMID   16685264.
  10. ↑ 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. PMC   2361309 . PMID   16685264.
  11. 1 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. PMC   2361309 . PMID   16685264.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.