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Review
. 2022 Jun 7:26:27-34.
doi: 10.1016/j.omto.2022.05.009. eCollection 2022 Sep 15.

Novel roles of METTL1/WDR4 in tumor via m7G methylation

Wenli Cheng  1 , Aili Gao  2 , Hui Lin  3 , Wenjuan Zhang  1
Affiliations
Review

Novel roles of METTL1/WDR4 in tumor via m7G methylation

Wenli Cheng et al. Mol Ther Oncolytics. .

Abstract

As one of the prevalent posttranscriptional modifications of RNA, N7-methylguanosine (m7G) plays essential roles in RNA processing, metabolism, and function, mainly regulated by the methyltransferase-like 1 (METTL1) and WD repeat domain 4 (WDR4) complex. Emerging evidence suggests that the METTL1/WDR4 complex promoted or inhibited the processes of many tumors, including head and neck, lung, liver, colon, bladder cancer, and teratoma, dependent on close m7G methylation modification of tRNA or microRNA (miRNA). Therefore, METTL1 and m7G modification can be used as biomarkers or potential intervention targets, providing new possibilities for early diagnosis and treatment of tumors. This review will mainly focus on the mechanisms of METTL1/WDR4 via m7G in tumorigenesis and the corresponding detection methods.

Keywords: METTL1; N7-methylguanosine; WDR4; tRNA; tumor.

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Conflict of interest statement

The authors declare that they do not have any conflicts of interest related to this study. This manuscript has been read and approved by all the authors and has not been submitted to or is not under consideration for publication elsewhere.

Figures

None
Graphical abstract
Figure 1
Figure 1
Diverse m7G sites and bio-effects mediated by RNA methyltransferases The m7G modification presents in 5′ cap of mRNA, 5′ UTR, and AG-rich regions of internal mRNA, G-rich regions of miRNA, position 46 of tRNA, and G1639 of 18s rRNA in humans. The bio-effects are mediated by different RNA methyltransferases, including RNMT, the METTL1/WDR4 complex, and the WBSCR22/TRMT112 complex, acting on mRNA stability, translation, and ribosomal biogenesis.
Figure 2
Figure 2
Mechanisms of METTL1/WDR4-m7G modification affecting tumorigenesis METTL1/WDR4-complex-mediated m7G regulates the processes of the tumor by targeting tRNA or miRNA. The m7G-modified tRNA causes the reduction of ribosome pausing and the elimination of ribosome collision-mediated translation inhibition, selectively promoting the translation of certain cell-cycle regulatory mRNAs, which are enriched in corresponding m7G-tRNA cognate codons, regulating the proliferation and differentiation of tumor cells. m7G modifies pri-miRNA directly to mature miRNA efficiency, inhibits the expression of oncogene, and then inhibits the proliferation and differentiation of tumor cells.
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