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METTL1 Promotes let-7 MicroRNA Processing via m7G Methylation
Open accessAbstract
7-methylguanosine (m7G) is present at mRNA caps and at defined internal positions within tRNAs and rRNAs. However, its detection within low-abundance mRNAs and microRNAs (miRNAs) has been hampered by a lack of sensitive detection strategies. Here, we adapt a chemical reactivity assay to detect internal m7G in miRNAs. Using this technique (Borohydride Reduction sequencing [BoRed-seq]) alongside RNA immunoprecipitation, we identify m7G within a subset of miRNAs that inhibit cell migration. We show that the METTL1 methyltransferase mediates m7G methylation within miRNAs and that this enzyme regulates cell migration via its catalytic activity. Using refined mass spectrometry methods, we map m7G to a single guanosine within the let-7e-5p miRNA. We show that METTL1-mediated methylation augments let-7 miRNA processing by disrupting an inhibitory secondary structure within the primary miRNA transcript (pri-miRNA). These results identify METTL1-dependent N7-methylation of guanosine as a new RNA modification pathway that regulates miRNA structure, biogenesis, and cell migration.
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“Furthermore, the ubiquitin-like domain within the ligase promotes ubiquitination of histone H3, which recruits DNMT1 to newly replicated chromatin to ensure the inheritance of DNA methylation 42 .”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [42]
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Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · cited 2×
“G Addgene #12259 pMirGlo Promega Cat# E1330 Software and Algorithms Bioconductor https://www.bioconductor.org/ N/A DESeq2 Love et al., 2014 N/A FastQC https://github.com/s-andrews/ FastQC N/A featureCounts Liao et al., 2014 N/A G4Hunter Bedrat et al., 2016 N/A Gage Luo et al., 2009 N/A gbm Freund and Schapire, 1997 N/…”
InfluentialTrimmomatic: a flexible trimmer for Illumina sequence data
Bolger, A. M., Lohse, M., & Usadel, B. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu170 · Cited by 65,548
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709
featureCounts: an efficient general purpose program for assigning sequence reads to genomic features
Liao, Y., Smyth, G. K., & Shi, W. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btt656 · Cited by 27,219
A decision-theoretic generalization of on-line learning and an application to boosting
Freund, Y., & Schapire, R. E. (1997) · Journal of Computer and System Sciences · doi:10.1006/jcss.1997.1504 · Cited by 20,466
MicroRNAs: Target Recognition and Regulatory Functions
Bartel, D. P. (2009) · Cell · doi:10.1016/j.cell.2009.01.002 · Cited by 20,068 · cited 1×
“Their specificity is mediated by partial base pairing to sequences predominantly found in the 30 UTR of mRNAs (Bartel, 2009).”
The nuclear RNase III Drosha initiates microRNA processing
Lee, Y., Ahn, C., Han, J., Choi, H., Kim, J., Yim, J., Lee, J., Provost, P., Rådmark, O., Kim, S., et al. (2003) · Nature · doi:10.1038/nature01957 · Cited by 5,292
Lorenz, R., Bernhart, S. H., Höner zu Siederdissen, C., Tafer, H., Flamm, C., Stadler, P. F., & Hofacker, I. L. (2011) · Algorithms for Molecular Biology · doi:10.1186/1748-7188-6-26 · Cited by 5,098
miRBase: annotating high confidence microRNAs using deep sequencing data
Kozomara, A., & Griffiths-Jones, S. (2014) · Nucleic Acids Research · doi:10.1093/nar/gkt1181 · Cited by 5,073
Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq
Dominissini, D., Moshitch-Moshkovitz, S., Schwartz, S., Salmon-Divon, M., Ungar, L., Osenberg, S., Cesarkas, K., Jacob-Hirsch, J., Amariglio, N., Kupiec, M., et al. (2012) · Nature · doi:10.1038/nature11112 · Cited by 4,884 · cited 2×
“, 2016], N6-methyladenosine [Dominissini et al., 2012], and 5-hydroxymethylcytosine [Delatte et al.”
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Barbieri, I., & Kouzarides, T. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-020-0253-2 · Cited by 1,350
Self-citationThe regulation and functions of DNA and RNA G-quadruplexes
Varshney, D., Spiegel, J., Zyner, K. G., Tannahill, D., & Balasubramanian, S. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0236-x · Cited by 1,292
Self-citationThe epitranscriptome beyond m6A
Wiener, D., & Schwartz, S. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-020-00295-8 · Cited by 733
The roles of DNA, RNA and histone methylation in ageing and cancer
Michalak, E. M., Burr, M. L., Bannister, A. J., & Dawson, M. A. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0143-1 · Cited by 549
Self-citationSmall and long non-coding RNAs: Past, present, and future
Chen, L., & Kim, V. N. (2024) · Cell · doi:10.1016/j.cell.2024.10.024 · Cited by 461
RNA modifications detection by comparative Nanopore direct RNA sequencing
Léger, A., Amaral, P., Pandolfini, L., Capitanchik, C., Capraro, F., Miano, V., Migliori, V., Toolan-Kerr, P., Sideri, T. C., Enright, A. J., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-27393-3 · Cited by 433
“qRT-PCR primers: 7sk (22-73): Fwd 5′-GCGACATCTGTCACCC CATT-3′; Rev 5′-CAGCCAGATCAGCCGAATCA-3′.”
Self-citationRNA modifications: importance in immune cell biology and related diseases
Cui, L., Ma, R., Cai, J., Guo, C., Chen, Z., Yao, L., Wang, Y., Fan, R., Wang, X., & Shi, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01175-9 · Cited by 432
“2 to 5 and Table 1).(135,150,151) As we know, m(7)G is widely present in mRNAs and is a critical regulator in the translation process, therefore, it may not be a good therapic target in human diseases.”
BackgroundEpigenetic regulation in the tumor microenvironment: molecular mechanisms and therapeutic targets
Yang, J., Xu, J., Wang, W. T., Zhang, B., Yu, X., & Shi, S. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01480-x · Cited by 412
“Among these complexes, METTL1 binds with its cofactor WDR4 to deposit an m(7)G mark on tRNAs, miRNAs, and mRNAs; thus, the METTL1/ WDR4 complex can impact tRNA function, promote miRNA biogenesis and regulate translation efficacy.(114,115,120,121) The WBSCR22/TRMT112 complex is critical for rRNA m(7)G modification.”
BackgroundRNA modifications in physiology and disease: towards clinical applications
Delaunay, S., Helm, M., & Frye, M. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-023-00645-2 · Cited by 368
METTL1-mediated m7G modification of Arg-TCT tRNA drives oncogenic transformation
Orellana, E. A., Liu, Q., Yankova, E., Pirouz, M., Braekeleer, E. D., Zhang, W. C., Lim, J., Aspris, D., Sendinc, E., Garyfallos, D. A., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.06.031 · Cited by 354
Quantitative profiling of pseudouridylation dynamics in native RNAs with nanopore sequencing
Begik, O., Lucas, M. C., Pryszcz, L. P., Ramírez, J. M., Medina, R., Milenkovic, I., Cruciani, S., Liu, H., Vieira, H. G. S., Sas‐Chen, A., et al. (2021) · Nature Biotechnology · doi:10.1038/s41587-021-00915-6 · Cited by 307
Dynamic methylome of internal mRNA N7-methylguanosine and its regulatory role in translation
Malbec, L., Zhang, T., Chen, Y., Zhang, Y., Sun, B., Shi, B., Zhao, Y., Yang, Y., & Yang, Y. (2019) · Cell Research · doi:10.1038/s41422-019-0230-z · Cited by 306
The potential role of N7-methylguanosine (m7G) in cancer
Luo, Y., Yao, Y., Wu, P. S., Zi, X., Sun, N., & He, J. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01285-5 · Cited by 257
“METTL1/ WDR4 promotes miRNA biogenesis by adding the m7G modification to the G-quadruplex structure of the primary miRNA transcript (pri-miRNA) [13].”
BackgroundSystems and Synthetic microRNA Biology: From Biogenesis to Disease Pathogenesis
Matsuyama, H., & Suzuki, H. I. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms21010132 · Cited by 258
“A recent report described that METTL1 mediates m7G methylation of the G-quadruplex motif in pri-miRNAs of an important tumor suppressive miRNA, let-7e, leading to the suppression of G-quadruplex formation and enhancement of Drosha processing [88]; the authors of that study also reported a new method for detection of m…”
BackgroundRNA methylation and cancer treatment
Yang, B., Wang, J., Tan, Y., Yuan, R., Chen, Z., & Zou, C. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105937 · Cited by 244
Xia, P., Zhang, H., Xu, K., Jiang, X. W., Gao, M., Wang, G., Liu, Y., Yao, Y., Chen, X., Ma, W., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03973-5 · Cited by 230
Detection of internal N7-methylguanosine (m7G) RNA modifications by mutational profiling sequencing
Enroth, C., Poulsen, L. D., Iversen, S., Kirpekar, F., Albrechtsen, A., & Vinther, J. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz736 · Cited by 228
“…publication by Pandolfini et al. , it was reported that a subset of human miRNAs are m 7 G modified, including Let-7e, for which the m 7 G modification was validated and localized to position 18 using mass spectroscopy of a RNase A fragment of the gel purified miRNA fraction (Figure 5A) (23).”
InfluentialRNA G-quadruplexes (rG4s): genomics and biological functions
Lyu, K., Chow, E. Y., Mou, X., Chan, T., & Kwok, C. K. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab187 · Cited by 216
“One initial study has shown that internal m7G in pre-miRNA precludes rG4 formation, resulting in mature miRNA regulation (231).”
BackgroundG-Quadruplexes in RNA Biology: Recent Advances and Future Directions
Dumas, L., Herviou, P., Dassi, E., Cammas, A., & Millevoi, S. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.11.001 · Cited by 210
“As METTL1 has been shown to be involved in lung cancer cell migration [45], RG4-forming sequences would confer METTL1 selectivity toward a specific pool of miRNAs regulating cellular processes linked to cancer development.”
BackgroundInfluentialWriters, readers and erasers of RNA modifications in cancer
Esteve‐Puig, R., Bueno-Costa, A., & Esteller, M. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.01.021 · Cited by 203
METTL3 Inhibitors for Epitranscriptomic Modulation of Cellular Processes
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QKI shuttles internal m7G-modified transcripts into stress granules and modulates mRNA metabolism
Zhao, Z., Qing, Y., Dong, L., Han, L., Wu, D., Li, Y., Li, W., Xue, J., Zhou, K., Sun, M., et al. (2023) · Cell · doi:10.1016/j.cell.2023.05.047 · Cited by 194
METTL1‐m7G‐EGFR/EFEMP1 axis promotes the bladder cancer development
Ying, X., Liu, B., Yuan, Z., Huang, Y., Chen, C., Xu, J., Zhang, H., Qi, D., Yang, S., Lin, S., et al. (2021) · Clinical and Translational Medicine · doi:10.1002/ctm2.675 · Cited by 188
Han, H., Yang, C., Ma, J., Zhang, S., Zheng, S., Ling, R., Sun, K., Guo, S., Huang, B., Liang, Y., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29125-7 · Cited by 183
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Qiu, L., Qian, J., Li, Y., & Han, J. (2023) · Molecular Biomedicine · doi:10.1186/s43556-023-00139-x · Cited by 182
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Kim, H., Lee, Y.-Y., & Kim, V. N. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00805-0 · Cited by 201
“METTL1 introduces 7-methylguanosine (m 7 G) into specific pri-miRNAs, including pri-let-7e 234 .”
Liu, W.-W., Zheng, S.-Q., Tian, L., Fei, Y.-F., Wang, C., Zhang, S., Wang, F., Jiang, G., & Wang, H. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01777-5 · Cited by 187
“157 At present, our understanding of m7G regulators is apparently limited.”
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RNA methylations in human cancers
Han, X., Wang, M., Zhao, Y., Yang, Y., & Yang, Y. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.11.007 · Cited by 159
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New Twists in Detecting mRNA Modification Dynamics
Anreiter, I., Mir, Q., Simpson, J. T., Janga, S. C., & Soller, M. (2020) · Trends in biotechnology · doi:10.1016/j.tibtech.2020.06.002 · Cited by 156
“For example, the m(7)G site in let-7 miRNA is in fact a fragment of rRNA with a well-known Gm site [59,60].”
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“The primary enzyme responsible for this modification is methyltransferase-like 1 (METTL1), which partners with the WD repeat domain 4 (WDR4) complex to insert m7G modifications into tRNA, miRNA, and mRNA, thus influencing miRNA structure and biogenesis [118, 119].”
BackgroundTang, Q., Li, L., Wang, Y., Wu, P., Hou, X., Ouyang, J., Fan, C., Li, Z., Wang, F., Guo, C. J., et al. (2023) · British Journal of Cancer · doi:10.1038/s41416-023-02275-1 · Cited by 151
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Teng, P., Liang, Y., Yarmishyn, A. A., Hsiao, Y., Lin, T.-Y., Lin, T.-W., Teng, Y., Yang, Y.-P., Wang, M., Chien, C., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910592 · Cited by 140
mRNA Regulation by RNA Modifications
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“It should also be noted that the terminal cap modification, m 7 G, has been identified as an internal mRNA modification by mass spectrometry and sequencing studies (52, 53).”
BackgroundSu, Z., Monshaugen, I., Wilson, B., Wang, F., Klungland, A., Ougland, R., & Dutta, A. (2022) · Nature Communications · doi:10.1038/s41467-022-29790-8 · Cited by 139
Liu, Y., Yang, C., Yong, Z., Chi, Q., Wang, Z., & Sun, B. (2019) · Aging · doi:10.18632/aging.102575 · Cited by 136
“Besides, miR-149-3p was the downstream target of METTL1 [10], and overexpression of miR-149-3p decreased chemoresistance of multiple cancers to”
BackgroundResultInfluentialThe diverse structural landscape of quadruplexes
Lightfoot, H., Hagen, T., Tatum, N., & Hall, J. (2019) · FEBS Letters · doi:10.1002/1873-3468.13547 · Cited by 114
Tian, Q., Zhang, M., Zeng, J.-S., Luo, R.-G., Wen, Y., Chen, J., Gan, L., & Xiong, J. (2019) · Journal of Molecular Medicine · doi:10.1007/s00109-019-01830-9 · Cited by 134
Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance
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Human transfer RNA modopathies: diseases caused by aberrations in transfer RNA modifications
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Writers, readers, and erasers RNA modifications and drug resistance in cancer
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“This modification involves the addition of a methyl group to the N7 position of ribo-guano-sine [157–160].”
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Qi, Y., Liu, Z., Hong, L., Li, P., & Ling, Z. (2023) · Journal of Hematology & Oncology · doi:10.1186/s13045-023-01477-7 · Cited by 127
“The METTL1 augments let-7 miRNA family processing by disrupting the repressive secondary structure, and the METTL1-mediated m7G modification serves as a novel RNA modification pathway in regulating biogenesis and cell migration [15].”
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Furlan, M., Delgado-Tejedor, A., Mulroney, L., Pelizzola, M., Novoa, E. M., & Leonardi, T. (2021) · RNA Biology · doi:10.1080/15476286.2021.1978215 · Cited by 111
“…the modified ribo-nucleotide [4,5,19–21]; and ii) chemical-based detection, using chemical compounds that will selectively react with the modified ribonucleotide of interest, followed by reverse transcription of the RNA fragment, leading to accumulation of reads with identical ends [22–28].”
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Yang, X. F., Liu, M., Li, M., Zhang, S., Hiju, H., Sun, J. P., Mao, Z., Zheng, M., & Feng, B. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01159-9 · Cited by 119
“showed that a subgroup of tumor suppressor miRNAs, including let-7e, contained m7G modification sites [91].”
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Wiese, M., & Bannister, A. J. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.01.006 · Cited by 122
“Importantly, the biosynthesis of the let-7 family of miRNAs is facilitated by METTL1 methyltransferase deposition of m7G within a quadruplex structure, as it promotes processing of the pri-miRNA [120].”
BackgroundSelf-citationMETTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer
García-Vílchez, R., Añazco-Guenkova, A. M., Dietmann, S., López, J., Morón-Calvente, V., D’Ambrosi, S., Nombela, P., Zamacola, K., Mendizabal, I., Garcia‐Longarte, S., et al. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01809-8 · Cited by 116
“In line with our findings, recent evidence has associated increased METTL1 expression with the occurrence of several cancer types [22, 23, 28, 29, 32–34, 36, 37, 96, 97].”
BackgroundResultSmall RNA modifications: regulatory molecules and potential applications
Xiong, Q., & Zhang, Y. (2023) · Journal of Hematology & Oncology · doi:10.1186/s13045-023-01466-w · Cited by 121
“For example, METTL1 binds directly to the miRNA precursor via m7G and accelerates miRNA maturation [168].”
BackgroundRNA modification in cardiovascular disease: implications for therapeutic interventions
Wang, C., Hou, X., Guan, Q., Zhou, H., Li, Z., Liu, L., Liu, J., Li, F., Li, W., & Liu, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01638-7 · Cited by 111
Deng, Y., Zhou, Z., Ji, W., Lin, S., & Wang, M. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-01814-4 · Cited by 104
“Recent studies have shown that METTL1-mediated m(7)G methylation is not restricted to tRNA but also occurs on mRNAs and miRNAs, increasing translation efficiency and miRNA processing, respectively [43, 44].”
BackgroundRMBase v3.0: decode the landscape, mechanisms and functions of RNA modifications
Xuan, J., Chen, L., Chen, Z., Pang, J., Huang, J., Lin, J., Zheng, L., Li, B., Qu, L., & Yang, J. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad1070 · Cited by 104
“For example, METTL1, an up-regulated RMP in CO AD , LUAD , LUSC, READ and STAD, consistent with its roles of reducing the migration ability of cancer cells by maintaining its high levels in CO AD , LUAD and LUSC ( 17 ).”
BackgroundMETTL6 is a tRNA m 3 C methyltransferase that regulates pluripotency and tumor cell growth
Ignatova, V. V., Kaiser, S., Ho, J., Bing, X., Stolz, P., Tan, Y. X., Lee, C. L., Gay, F. P. H., Lastres, P. R., Gerlini, R., et al. (2020) · Science Advances · doi:10.1126/sciadv.aaz4551 · Cited by 102
“It has been shown that METTL1 catalyzes 7-methylguanosine (m 7 G) formation in microRNAs ( 15 ) and transfer RNA (tRNAs) ( 10 ).”
Novel roles of METTL1/WDR4 in tumor via m7G methylation
Cheng, W., Gao, A., Lin, H. M., & Zhang, W. (2022) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2022.05.009 · Cited by 97
“However, there was a study that found that the level of m(7)Gmodification had not been dramatically affected in tRNAs after reducing the level ofMETTL1.(19) It pointed out thatMETTL1 inhibited the progression of lung cancer.”
InfluentialIntegrative analyses of the RNA modification machinery reveal tissue- and cancer-specific signatures
Begik, O., Lucas, M. C., Liu, H., Ramírez, J. M., Mattick, J. S., & Novoa, E. M. (2020) · Genome biology · doi:10.1186/s13059-020-02009-z · Cited by 90
Cheray, M., Etcheverry, A., Jacques, C., Pacaud, R., Bougras-Cartron, G., Aubry, M., Denoual, F., Peterlongo, P., Nadaradjane, A., Briand, J., et al. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01155-z · Cited by 95
Liu, Z., Gao, L., Cheng, L., Lv, G., Sun, B., Wang, G., & Tang, Q. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-00944-y · Cited by 91
Internal m7G methylation: A novel epitranscriptomic contributor in brain development and diseases
Xia, X., Wang, Y., & Zheng, J. (2023) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2023.01.003 · Cited by 87
Novel insights into the emerging roles of tRNA-derived fragments in mammalian development
Guzzi, N., & Bellodi, C. (2020) · RNA Biology · doi:10.1080/15476286.2020.1732694 · Cited by 78
“function as recently proposed for other types of small RNAs [75,76].”
BackgroundSahafnejad, Z., Ramazi, S., & Allahverdi, A. (2023) · Genes · doi:10.3390/genes14040873 · Cited by 73
“demonstrated that a class of tumor suppressor miRNAs, such as let-7e, contain m7G modification sites using borhydride reduction sequencing (BoRed-seq) and mass spectrometry technology [16].”
MethodLiang, H., Jiao, Z., Rong, W., Qu, S., Liao, Z., Sun, X., Wei, Y., Zhao, Q., Wang, J., Liu, Y., et al. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa504 · Cited by 21
“There are different kinds of modification of miRNAs, including 2′-O-methylation (10) and m7G (11), which all can affect miRNA biogenesis and functions thereby playing a role in miRNA-based gene regulation network (10,11).”
BackgroundRole of N7-methylguanosine (m7G) in cancer
Chen, Y., Lin, H., Miao, L., & He, J. (2022) · Trends in Cell Biology · doi:10.1016/j.tcb.2022.07.001 · Cited by 72
Biological roles of RNA m7G modification and its implications in cancer
Zhang, X., Zhu, W., Shen, S., Shen, J., & Chen, X.-D. (2023) · Biology Direct · doi:10.1186/s13062-023-00414-5 · Cited by 72
“Additionally, METTL1 inhibits the proliferation and autophagy of A549 cells through the AKT/mTORC1 signaling pathway [6].”
BackgroundInfluentialContext-Dependent Roles of RNA Modifications in Stress Responses and Diseases
Wilkinson, E., Cui, Y., & He, Y. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041949 · Cited by 70
Liu, Y., Zhang, Y., Chi, Q., Wang, Z., & Sun, B. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117480 · Cited by 63
RetractedWang, L., Xue, Y., Li, H., Huo, R., Yan, Z., Wang, J., Xu, H., Wang, J., Cao, Y. B., & Zhao, J. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15101 · Cited by 62
Analysis of RNA Modifications by Second- and Third-Generation Deep Sequencing: 2020 Update
Motorin, Y., & Marchand, V. (2021) · Genes · doi:10.3390/genes12020278 · Cited by 63
“The same NaBH4 reduction of m7G was used for its profiling in human miRNAs, but the resulting RNA abasic site was used for Schiff base formation with Biotin-ARP (Aldehyde Reactive Probe) reagent containing the reactive NH2 group for the selective enrichment of the modified sites (Borohydride Reduction sequencing, BoRe…”
MethodZhu, S., Wu, Y., Zhang, X., Peng, S., Xiao, H., Chen, S., Xu, L., Su, T., & Kuang, M. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.08.004 · Cited by 63
He, M., Wang, Y., Xie, J., Pu, J., Shen, Z., Wang, A., Li, T., Wang, T., Li, G., Liu, Y., et al. (2023) · Oncogene · doi:10.1038/s41388-023-02882-5 · Cited by 63
Instrumental analysis of RNA modifications
Yoluç, Y., Ammann, G., Barraud, P., Jora, M., Limbach, P. A., Motorin, Y., Marchand, V., Tisné, C., Borland, K. M., & Kellner, S. M. (2021) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2021.1887807 · Cited by 59
“…al. 2019), pseudouridine (Carlile et al. 2014; Lovejoy et al. 2014; Schwartz et al. 2014; Li et al. 2015), 1-methyladenosine (Dominissini et al. 2016; Safra et al. 2017), 4-acetylcytidine (Thomas et al. 2018; Sas-Chen et al. 2020), and 7-methylguanosine (Enroth et al. 2019; Pandolfini et al. 2019).”
Zhang, M., Kan, D., Zhang, B., Chen, X., Wang, C., Chen, S., Gao, W., Yang, Z., Li, Y., Chen, Y., et al. (2023) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-023-02777-z · Cited by 60
“Moreover, the METTL1/WDR4 complex promotes the maturation of miRNA let-7e processing through its m7G methyltransferase activity, which subsequently module the ability of cell migration [29].”
BackgroundDysregulations of Functional RNA Modifications in Cancer, Cancer Stemness and Cancer Therapeutics
Uddin, M. B., Wang, Z., & Yang, C. (2020) · Theranostics · doi:10.7150/thno.41687 · Cited by 60
“occurring most commonly in position 46 of the tRNAs in both yeast and human and position 1639 of the 18S subunit of the human rRNA [70-72].”
Backgroundm 7 G-quant-seq: Quantitative Detection of RNA Internal N 7 -Methylguanosine
Zhang, L., Ju, C., Liu, C., Wei, J., Dai, Q., Chen, L., Ye, C., & He, C. (2022) · ACS Chemical Biology · doi:10.1021/acschembio.2c00792 · Cited by 59
Live single-cell transcriptional dynamics via RNA labelling during the phosphate response in plants
Hani, S., Cuyas, L., David, P., Secco, D., Whelan, J., Thibaud, M., Merret, R., Mueller, F., Pochon, N., Javot, H., et al. (2021) · Nature Plants · doi:10.1038/s41477-021-00981-3 · Cited by 59
Visualizing a protonated RNA state that modulates microRNA-21 maturation
Baisden, J. T., Boyer, J. A., Zhao, B., Hammond, S. M., & Zhang, Q. (2020) · Nature Chemical Biology · doi:10.1038/s41589-020-00667-5 · Cited by 56
Zhou, W., Wang, X., Chang, J., Cheng, C., & Miao, C. (2021) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408363.2021.2002256 · Cited by 58
Recognition of G-quadruplex RNA by a crucial RNA methyltransferase component, METTL14
Yoshida, A., Oyoshi, T., Suda, A., Futaki, S., & Imanishi, M. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab1211 · Cited by 57
THRONE: A New Approach for Accurate Prediction of Human RNA N7-Methylguanosine Sites
Shoombuatong, W., Basith, S., Pitti, T., Lee, G., & Manavalan, B. (2022) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167549 · Cited by 58
Wong, J. M., & Eirin-Lopez, J. M. (2021) · Molecular Biology and Evolution · doi:10.1093/molbev/msab267 · Cited by 57
“METTL1, the only METTL protein known to contribute methylguanosine, forms N(7)-methylguanosine (m(7)G) in tRNA, mRNA, and miRNA (Okamoto et al. 2014; Pandolfini et al. 2019; Zhang et al. 2019).”
BackgroundPathological and Therapeutic Advances in Parkinson’s Disease: Mitochondria in the Interplay
Naren, P., Cholkar, A., Kamble, S., Khan, S. S., Srivastava, S., Madan, J., Mehra, N. K., Tiwari, V., Singh, S. B., & Khatri, D. K. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220682 · Cited by 60
Zhu, D., Zeng, S., Su, C., Li, J., Xuan, Y., Lin, Y., Xu, E., & Fan, Q. (2024) · Clinical Epigenetics · doi:10.1186/s13148-024-01633-x · Cited by 55
“…enable high-throughput methylation site detection and accurate identification of various DNA/RNA methylation patterns, such as m5c, m6a, m7g [78–80]; these technologies also function as tumor biomarkers to inform precise disease subtyping and customized treatment [81]; concerning modification…”
BackgroundRNA modification systems as therapeutic targets
Zhang, L., Wei, J., Zou, Z., & He, C. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-025-01280-8 · Cited by 64
Galloway, A., Atrih, A., Grzela, R., Darżynkiewicz, E., Ferguson, M. A. J., & Cowling, V. H. (2020) · Open Biology · doi:10.1098/rsob.190306 · Cited by 56
“Recent studies have detected internal m7G in mRNA, which compromises the use of anti-7-methylguanosine antibodies for cap detection [32,33].”
BackgroundRNA G-quadruplex regulates microRNA-26a biogenesis and function
Liu, G., Du, W., Xu, H., Sun, Q., Tang, D., Zou, S., Zhang, Y., Ma, M., Zhang, G., Du, X., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.02.032 · Cited by 55
Jones, A. N., Tikhaia, E., Mourão, A., & Sattler, M. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac080 · Cited by 54
“As has been demonstrated in several studies, RNA modifications increase the diversity of RNA function, influencing the regulation of numerous biological processes that include pre-mRNA splicing, mRNA translation, and RNA export and stability (1,4,10,11,13,57,58).”
Shao, D., Li, Y., Wu, J., Zhang, B., Xie, S., Zheng, X., & Jiang, Z. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.903117 · Cited by 53
“Typical enzymes involved in regulating internal m7G methylation include methyltransferase-like 1 (the YEAST enzyme homolog of TRMT8) and its co-factor, WDR4, which catalyzes m7G modification at G46 of specific tRNAs, such as tRNAPhe (Pandolfini et al., 2019).”
BackgroundLi, J., Yue, S., Gao, Z., Hu, W., Liu, Z., Xu, G., Wu, Z., Zhang, X., Zhang, G., Qian, F., et al. (2023) · Analytical Chemistry · doi:10.1021/acs.analchem.3c01630 · Cited by 54
Chen, X., Li, X., Xu, S., Hu, S., Wang, T., Li, R., Liu, C.-Y., Xue, J., Zhou, L., Wang, Y.-H., et al. (2023) · Cell Death and Differentiation · doi:10.1038/s41418-023-01179-0 · Cited by 53
“Additionally, METTL1-dependent N7-methylation of guanosine regulates miRNA structure, biogenesis, and cell migration [41].”
BackgroundAdvances in targeting RNA modifications for anticancer therapy
Pomaville, M. M., & He, C. (2023) · Trends in cancer · doi:10.1016/j.trecan.2023.04.003 · Cited by 52
Transfer RNAs as dynamic and critical regulators of cancer progression
Pinzaru, A. M., & Tavazoie, S. F. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-023-00611-4 · Cited by 54
“Moreover, METTL1, as well as most tRNA-modifying enzymes, can act on other RNA species, such as mRNAs and microRNAs (miRNAs), apart from tRNAs 24,86,87 .”
BackgroundPrognostic role of METTL1 in glioma
Li, L., Yang, Y., Wang, Z., Xu, C., Huang, J., & Li, G. (2021) · Cancer Cell International · doi:10.1186/s12935-021-02346-4 · Cited by 49
“Furthermore, m7G methylation has been known to increase translation efficiency and microRNA processing [44, 45].”
BackgroundZhou, W., Wang, C., Chang, J., Huang, Y., Xue, Q., Miao, C., & Wu, P. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.722728 · Cited by 46
“METTL1 mediated methylation enhances the let-7 miRNA processing by destroying the inhibitory secondary structure in pri-miRNA transcripts (Pandolfini et al., 2019).”
BackgroundJiang, H., Gao, Y., Zhang, L., Chen, D., Gan, J., & Murchie, A. I. H. (2021) · Nature Catalysis · doi:10.1038/s41929-021-00685-z · Cited by 50
The EDC4‐XRN1 interaction controls P‐body dynamics to link mRNA decapping with decay
Brothers, W. R., Ali, F. N., Kajjo, S., & Fabian, M. R. (2023) · The EMBO Journal · doi:10.15252/embj.2023113933 · Cited by 45
Perturbation of METTL1-mediated tRNA N7- methylguanosine modification induces senescence and aging
Fu, Y., Jiang, F., Zhang, X., Pan, Y., Xu, R., Liang, X. H., Wu, X., Li, X., Lin, K., Shi, R., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49796-8 · Cited by 49
The epitranscriptome of small non-coding RNAs
Li, X., Peng, J., & Yi, C. (2021) · Non-coding RNA Research · doi:10.1016/j.ncrna.2021.10.002 · Cited by 47
Yu, S., Sun, Z., Ju, T., Liu, Y., Mei, Z., Wang, C., Qu, Z., Li, N., Wu, F., Liu, K., et al. (2024) · Advanced Science · doi:10.1002/advs.202308769 · Cited by 44
A Comprehensive Analysis of METTL1 to Immunity and Stemness in Pan-Cancer
Gao, Z., Xu, J., Zhang, Z., Yang, F., Xue, H., Guo, X. H., Deng, L., Wang, S., Zhao, R., Zhang, P., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.795240 · Cited by 44
“In addition, METTL1dependent m(7)G regulates miRNA structure and biogenesis (4).”
BackgroundTorsin, L. I., Petrescu, G. E. D., Sabo, A. A., Chen, B., Brehar, F. M., Dragomir, M. P., & Călin, G. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020581 · Cited by 44
Wang, C., Wang, W., Han, X., Du, L., Li, A., & Huang, G. (2021) · Oncology Letters · doi:10.3892/ol.2021.12591 · Cited by 43
“Furthermore, METTL1 promotes miRNA processing in A549 cells to suppress cell migration (9), whereas its overexpression promotes hepatocellular carcinoma (HCC) and is associated with poor prognosis (12).”
BackgroundInfluential
Metadata
- Authors
- Pandolfini, L., Barbieri, I., Bannister, A. J., Hendrick, A., Andrews, B., Webster, N., Murat, P., Mach, P., Brandi, R., Robson, S. C., Migliori, V., Alendar, A., d’Onofrio, M., Balasubramanian, S., & Kouzarides, T.
- Affiliations
- University of Cambridge (GB)
- European Brain Research Institute (IT)
- Istituto di Farmacologia Traslazionale (IT)
- Corresponding author
- Kouzarides, Tony
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 74
- Issue
- 6
- Pages
- 1278-1290.e9
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC6591002
- OpenAlex
- W2941132662
- Cited by
- 491
- References
- 66
- Citations by year
- 2026: 32 · 2025: 68 · 2024: 76 · 2023: 95 · 2022: 101 · 2021: 68 · 2020: 37 · 2019: 14
- FWCI
- 18.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
- Apollo
- Funders
- European Research Council (268569)
- Cancer Research UK (RG72100)
- Horizon 2020 (732678)
- Wellcome Trust (WT203144, C6946/A24843)
- Kay Kendall Leukaemia Fund (337778, RG86786, RG88664)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- METTL1, let-7 microRNA, 7-methylguanosine, RNA methylation, microRNA biogenesis, cell migration, RNA modification
- MeSH terms
- A549 Cells, Base Sequence, Biological Assay, Cell Movement, Guanosine, Humans, Methylation, Methyltransferases, Nucleic Acid Conformation, RNA Processing, Post-Transcriptional, Caco-2 Cells, MicroRNAs, Cell Proliferation, HEK293 Cells
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