7-Methylguanosine is a modified form of the purine nucleotides. When present in human urine, it may be a biomarker for certain cancers.
Reference Reading
1. 7-Methylguanosine Modifications in Transfer RNA (tRNA)
Chie Tomikawa. Int J Mol Sci. 2018 Dec 17;19(12):4080. doi: 10.3390/ijms19124080.
More than 90 different modified nucleosides have been identified in tRNA. Among the tRNA modifications, the 7-methylguanosine (m⁷G) modification is found widely in eubacteria, eukaryotes, and a few archaea. In most cases, the m⁷G modification occurs at position 46 in the variable region and is a product of tRNA (m⁷G46) methyltransferase. The m⁷G46 modification forms a tertiary base pair with C13-G22, and stabilizes the tRNA structure. A reaction mechanism for eubacterial tRNA m⁷G methyltransferase has been proposed based on the results of biochemical, bioinformatic, and structural studies. However, an experimentally determined mechanism of methyl-transfer remains to be ascertained. The physiological functions of m⁷G46 in tRNA have started to be determined over the past decade. For example, tRNA m⁷G46 or tRNA (m⁷G46) methyltransferase controls the amount of other tRNA modifications in thermophilic bacteria, contributes to the pathogenic infectivity, and is also associated with several diseases. In this review, information of tRNA m⁷G modifications and tRNA m⁷G methyltransferases is summarized and the differences in reaction mechanism between tRNA m⁷G methyltransferase and rRNA or mRNA m⁷G methylation enzyme are discussed.
2. The potential role of N7-methylguanosine (m7G) in cancer
Yuejun Luo, Yuxin Yao, Peng Wu, Xiaohui Zi, Nan Sun, Jie He. J Hematol Oncol. 2022 May 19;15(1):63. doi: 10.1186/s13045-022-01285-5.
N7-methylguanosine (m7G), one of the most prevalent RNA modifications, has recently attracted significant attention. The m7G modification actively participates in biological and pathological functions by affecting the metabolism of various RNA molecules, including messenger RNA, ribosomal RNA, microRNA, and transfer RNA. Increasing evidence indicates a critical role for m7G in human disease development, especially cancer, and aberrant m7G levels are closely associated with tumorigenesis and progression via regulation of the expression of multiple oncogenes and tumor suppressor genes. Currently, the underlying molecular mechanisms of m7G modification in cancer are not comprehensively understood. Here, we review the current knowledge regarding the potential function of m7G modifications in cancer and discuss future m7G-related diagnostic and therapeutic strategies.
3. N7-Methylguanosine tRNA modification enhances oncogenic mRNA translation and promotes intrahepatic cholangiocarcinoma progression
Zihao Dai, Haining Liu, Junbin Liao, Cheng Huang, Xiaoxue Ren, Wanjie Zhu, Shenghua Zhu, Baogang Peng, Shaoqiang Li, Jiaming Lai, Lijian Liang, Lixia Xu, Sui Peng, Shuibin Lin, Ming Kuang. Mol Cell. 2021 Aug 19;81(16):3339-3355.e8. doi: 10.1016/j.molcel.2021.07.003.
Cancer cells selectively promote translation of specific oncogenic transcripts to facilitate cancer survival and progression, but the underlying mechanisms are poorly understood. Here, we find that N7-methylguanosine (m7G) tRNA modification and its methyltransferase complex components, METTL1 and WDR4, are significantly upregulated in intrahepatic cholangiocarcinoma (ICC) and associated with poor prognosis. We further reveal the critical role of METTL1/WDR4 in promoting ICC cell survival and progression using loss- and gain-of-function assays in vitro and in vivo. Mechanistically, m7G tRNA modification selectively regulates the translation of oncogenic transcripts, including cell-cycle and epidermal growth factor receptor (EGFR) pathway genes, in m7G-tRNA-decoded codon-frequency-dependent mechanisms. Moreover, using overexpression and knockout mouse models, we demonstrate the crucial oncogenic function of Mettl1-mediated m7G tRNA modification in promoting ICC tumorigenesis and progression in vivo. Our study uncovers the important physiological function and mechanism of METTL1-mediated m7G tRNA modification in the regulation of oncogenic mRNA translation and cancer progression.
