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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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× · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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× · see citing works
“Their specificity is mediated by partial base pairing to sequences predominantly found in the 30 UTR of mRNAs (Bartel, 2009).”
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 · see citing works
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 5,094 · see citing works
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× · see citing works
“, 2016], N6-methyladenosine [Dominissini et al., 2012], and 5-hydroxymethylcytosine [Delatte et al.”
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 4,629 · see citing works
Bartel, D. P. (2018) · Cell · doi:10.1016/j.cell.2018.03.006 · Cited by 3,751 · cited 1× · see citing works
“…physiological and pathological processes. miRNA biosynthesis is complex and involves a multistep pathway that can be regulated at many levels (Bartel, 2018), including post-transcriptional modification of miRNA precursors (Alarcón et al., 2015; Xhemalce et al., 2012). miRNAs are synthesized…”
BackgroundDynamic RNA Modifications in Gene Expression Regulation
Roundtree, I. A., Evans, M., Pan, T., & He, C. (2017) · Cell · doi:10.1016/j.cell.2017.05.045 · Cited by 3,459 · see citing works
Regulation of mRNA Translation and Stability by microRNAs
Fabian, M. R., Sonenberg, N., & Filipowicz, W. (2010) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060308-103103 · Cited by 3,214 · see citing works
MicroRNA maturation: stepwise processing and subcellular localization
Lee, Y., Jeon, K., Lee, J., Kim, S., & Kim, V. N. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf476 · Cited by 2,468 · see citing works
Small silencing RNAs: an expanding universe
Ghildiyal, M., & Zamore, P. D. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2504 · Cited by 2,314 · see citing works
TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing
Chendrimada, T. P., Gregory, R. I., Kumaraswamy, E., Norman, J. A., Cooch, N. S., Nishikura, K., & Shiekhattar, R. (2005) · Nature · doi:10.1038/nature03868 · Cited by 2,103 · see citing works
Normalization of cDNA microarray data
Smyth, G. K., & Speed, T. (2003) · Methods · doi:10.1016/s1046-2023(03)00155-5 · Cited by 1,871 · see citing works
Circular dichroism and conformational polymorphism of DNA
Kypr, J., Kejnovská, I., Renčiuk, D., & Vorlı́čková, M. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp026 · Cited by 1,782 · see citing works
The Encyclopedia of DNA elements (ENCODE): data portal update
Davis, C. A., Hitz, B. C., Sloan, C. A., Chan, E. T., Davidson, J. M., Gabdank, I., Hilton, J. A., Jain, K., Baymuradov, U. K., Narayanan, A. K., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gkx1081 · Cited by 1,717 · see citing works
Prevalence of quadruplexes in the human genome
Huppert, J., & Balasubramanian, S. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki609 · Cited by 1,655 · see citing works
Self-citationUse of within-array replicate spots for assessing differential expression in microarray experiments
Smyth, G. K., Michaud, J., & Scott, H. S. (2005) · Computer applications in the biosciences · doi:10.1093/bioinformatics/bti270 · Cited by 1,406 · see citing works
N6-methyladenosine marks primary microRNAs for processing
Alarcón, C. R., Lee, H., Goodarzi, H., Halberg, N., & Tavazoie, S. F. (2015) · Nature · doi:10.1038/nature14281 · Cited by 1,394 · see citing works
miRWalk2.0: a comprehensive atlas of microRNA-target interactions
Dweep, H., & Gretz, N. (2015) · Nature Methods · doi:10.1038/nmeth.3485 · Cited by 1,343 · see citing works
GAGE: generally applicable gene set enrichment for pathway analysis
Luo, W., Friedman, M. S., Shedden, K., Hankenson, K. D., & Woolf, P. J. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-161 · Cited by 1,333 · see citing works
The tumor suppressor microRNA let-7 represses the HMGA2 oncogenePreprint
Lee, Y. S., & Dutta, A. (2007) · Genes & Development · doi:10.1101/gad.1540407 · Cited by 1,155 · see citing works
Disrupting the Pairing Between let-7 and Hmga2 Enhances Oncogenic Transformation
Mayr, C., Hemann, M. T., & Bartel, D. P. (2007) · Science · doi:10.1126/science.1137999 · Cited by 1,099 · see citing works
The dynamic N1-methyladenosine methylome in eukaryotic messenger RNA
Dominissini, D., Nachtergaele, S., Moshitch-Moshkovitz, S., Peer, E., Kol, N., Ben-Haim, M. S., Dai, Q., Segni, A. D., Salmon‐Divon, M., Clark, W. C., et al. (2016) · Nature · doi:10.1038/nature16998 · Cited by 1,026 · see citing works
Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells
Carlile, T. M., Rojas-Durán, M. F., Zinshteyn, B., Shin, H., Bartoli, K. M., & Gilbert, W. V. (2014) · Nature · doi:10.1038/nature13802 · Cited by 1,004 · cited 1× · see citing works
“, 2016]) or chemical reactivity of the modification (for pseudouridine [Carlile et al., 2014; Schwartz et al., 2014], m5C [Schaefer, 2015], and 2 0-O-methylation [Dai et al.”
BackgroundMODOMICS: a database of RNA modification pathways—2013 update
Machnicka, M. A., Milanowska, K., Oglou, O. O., Purta, E., Kurkowska, M., Olchowik, A., Januszewski, W., Kalinowski, S., Dunin-Horkawicz, S., Rother, K. M., et al. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1007 · Cited by 1,003 · see citing works
Transcriptome-wide Mapping Reveals Widespread Dynamic-Regulated Pseudouridylation of ncRNA and mRNA
Schwartz, S., Bernstein, D. A., Mumbach, M. R., Jovanović, M., Herbst, R. H., León-Ricardo, B. X., Engreitz, J., Guttman, M., Satija, R., Lander, E. S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.08.028 · Cited by 1,001 · cited 1× · see citing works
“…et al., 2016], N6-methyladenosine [Dominissini et al., 2012], and 5-hydroxymethylcytosine [Delatte et al., 2016]) or chemical reactivity of the modification (for pseudouridine [Carlile et al., 2014; Schwartz et al., 2014], m5C [Schaefer, 2015], and 2 0-O-methylation [Dai et al., 2017]).”
Lin28 Mediates the Terminal Uridylation of let-7 Precursor MicroRNA
Heo, I., Joo, C., Cho, J., Ha, M., Han, J., & Kim, V. N. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.09.014 · Cited by 947 · see citing works
Direct chemical method for sequencing RNA.
Peattie, D. A. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.4.1760 · Cited by 943 · cited 1× · see citing works
“This reaction is the basis of direct RNA sequencing (RNA-seq) by the Maxam and Gilbert method (Peattie, 1979) and has been used formappingm7G residues in highly abundant rRNAs and tRNAs at single nucleotide resolution (Zueva et al., 1985).”
MethodLandthaler, M., Yalçin, A., & Tuschl, T. (2004) · Current Biology · doi:10.1016/j.cub.2004.11.001 · Cited by 935 · see citing works
Therapeutic miRNA and siRNA: Moving from Bench to Clinic as Next Generation Medicine
Chakraborty, C., Sharma, A. R., Sharma, G., Doss, C. G. P., & Lee, S. (2017) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2017.06.005 · Cited by 731 · see citing works
An unconventional role for miRNA: let-7 activates toll-like receptor 7 and causes neurodegeneration
Lehmann, S. M., Krüger, C., Park, B., Derkow, K., Rosenberger, K., Baumgart, J., Trimbuch, T., Eom, G., Hinz, M., Kaul, D., et al. (2012) · Nature Neuroscience · doi:10.1038/nn.3113 · Cited by 697 · see citing works
Re-evaluation of G-quadruplex propensity with G4Hunter
Bedrat, A., Lacroix, L., & Mergny, J. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw006 · Cited by 693 · see citing works
5'-UTR RNA G-quadruplexes: translation regulation and targeting
Bugaut, A., & Balasubramanian, S. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks068 · Cited by 643 · see citing works
Self-citationDistinct roles of Akt1 and Akt2 in regulating cell migration and epithelial–mesenchymal transition
Irie, H. Y., Pearline, R. V., Grueneberg, D. A., Hsia, M., Ravichandran, P., Kothari, N. H., Natesan, S., & Brugge, J. S. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200505087 · Cited by 582 · see citing works
Lin, S., Liu, Q., Lelyveld, V. S., Choe, J., Szostak, J. W., & Gregory, R. I. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.06.001 · Cited by 486 · see citing works
The LIN28/let-7 Pathway in Cancer
Balzeau, J. C., Menezes, M. R., Cao, S., & Hagan, J. P. (2017) · Frontiers in Genetics · doi:10.3389/fgene.2017.00031 · Cited by 451 · see citing works
Transcriptome-wide distribution and function of RNA hydroxymethylcytosine
Delatte, B., Wang, F., Ngoc, L. V., Collignon, É., Bonvin, E., Deplus, R., Calonne, E., Hassabi, B., Putmans, P., Awe, S., et al. (2016) · Science · doi:10.1126/science.aac5253 · Cited by 441 · cited 1× · see citing works
“…antibodies (e.g., against N1-methyladenosine [Dominissini et al., 2016], N6-methyladenosine [Dominissini et al., 2012], and 5-hydroxymethylcytosine [Delatte et al., 2016]) or chemical reactivity of the modification (for pseudouridine [Carlile et al., 2014; Schwartz et al., 2014], m5C [Schaefer,…”
BackgroundPathview Web: user friendly pathway visualization and data integration
Luo, W., Pant, G., Bhavnasi, Y. K., Blanchard, S. G., & Brouwer, C. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx372 · Cited by 440 · see citing works
rG4-seq reveals widespread formation of G-quadruplex structures in the human transcriptome
Kwok, C. K., Marsico, G., Sahakyan, A. B., Chambers, V. S., & Balasubramanian, S. (2016) · Nature Methods · doi:10.1038/nmeth.3965 · Cited by 426 · see citing works
Self-citationTwo proteins that form a complex are required for 7-methylguanosine modification of yeast tRNA
Alexandrov, A., Martzen, M. R., & Phizicky, E. M. (2002) · RNA · doi:10.1017/s1355838202024019 · Cited by 371 · see citing works
Lin28 Enhances Tissue Repair by Reprogramming Cellular Metabolism
Shyh‐Chang, N., Zhu, H., de Soysa, Y., Shinoda, G., Seligson, M. T., Tsanov, K. M., Nguyen, L. H., Asara, J. M., Cantley, L. C., & Daley, G. Q. (2013) · Cell · doi:10.1016/j.cell.2013.09.059 · Cited by 362 · see citing works
Nm-seq maps 2′-O-methylation sites in human mRNA with base precision
Dai, Q., Moshitch-Moshkovitz, S., Han, D., Kol, N., Amariglio, N., Rechavi, G., Dominissini, D., & He, C. (2017) · Nature Methods · doi:10.1038/nmeth.4294 · Cited by 292 · see citing works
Detecting microRNA binding and siRNA off-target effects from expression data
van Dongen, S., Abreu‐Goodger, C., & Enright, A. J. (2008) · Nature Methods · doi:10.1038/nmeth.1267 · Cited by 274 · see citing works
Capturing the interactome of newly transcribed RNA
Bao, X., Guo, X., Yin, M., Tariq, M., Lai, Y., Kanwal, S., Zhou, J., Li, N., Lv, Y., Pulido-Quetglas, C., et al. (2018) · Nature Methods · doi:10.1038/nmeth.4595 · Cited by 222 · see citing works
The 3D rRNA modification maps database: with interactive tools for ribosome analysis
Piekna‐Przybylska, D., Decatur, W. A., & Fournier, M. J. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm855 · Cited by 215 · see citing works
Genome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasis
Zhang, H., Hao, Y., Yang, J., Zhou, Y., Li, J., Yin, S., Sun, C., Ma, M., Huang, Y., & Xi, J. (2011) · Nature Communications · doi:10.1038/ncomms1555 · Cited by 201 · see citing works
Structure and Function of Noncanonical Nucleobases
Carell, T., Brandmayr, C., Hienzsch, A., Müller, M., Pearson, D., Reiter, V., Thoma, I., Thumbs, P., & Wagner, M. (2012) · Angewandte Chemie International Edition · doi:10.1002/anie.201201193 · Cited by 190 · see citing works
Polysome Fractionation to Analyze mRNA Distribution Profiles
Panda, A. C., Martindale, J. L., & Gorospe, M. (2017) · BIO-PROTOCOL · doi:10.21769/bioprotoc.2126 · Cited by 165 · see citing works
Human RNA Methyltransferase BCDIN3D Regulates MicroRNA Processing
Xhemalçe, B., Robson, S. C., & Kouzarides, T. (2012) · Cell · doi:10.1016/j.cell.2012.08.041 · Cited by 153 · see citing works
Self-citationA Potassium Ion-Dependent RNA Structural Switch Regulates Human Pre-miRNA 92b Maturation
Arachchilage, G. M., Dassanayake, A. C., & Basu, S. (2015) · Chemistry & Biology · doi:10.1016/j.chembiol.2014.12.013 · Cited by 122 · see citing works
Structural Analysis using SHALiPE to Reveal RNA G‐Quadruplex Formation in Human Precursor MicroRNA
Kwok, C. K., Sahakyan, A. B., & Balasubramanian, S. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201603562 · Cited by 112 · see citing works
Self-citationThe tRNA methylase METTL1 is phosphorylated and inactivated by PKB and RSK in vitro and in cells
Cartlidge, R. A., Knebel, A., Peggie, M. W., Alexandrov, A., Phizicky, E. M., & Cohen, P. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600648 · Cited by 99 · cited 1× · see citing works
“Notably, AKT has been shown to directly phosphorylate METTL1 to inhibit its enzymatic activity (Cartlidge et al., 2005).”
BackgroundThe RNA Stem–Loop to G-Quadruplex Equilibrium Controls Mature MicroRNA Production inside the Cell
Pandey, S., Agarwala, P., Jayaraj, G. G., Gargallo, R., & Maiti, S. (2015) · Biochemistry · doi:10.1021/acs.biochem.5b00574 · Cited by 84 · see citing works
Methylation of deoxyribonucleic acid by diazomethane
Kriek, E., & Emmelot, P. (1964) · Biochimica et Biophysica Acta (BBA) - Specialized Section on Nucleic Acids and Related Subjects · doi:10.1016/0926-6550(64)90170-7 · Cited by 78 · see citing works
RNA 5-Methylcytosine Analysis by Bisulfite Sequencing
Schaefer, M. (2015) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2015.03.007 · Cited by 64 · cited 2× · see citing works
“…et al., 2016], N6-methyladenosine [Dominissini et al., 2012], and 5-hydroxymethylcytosine [Delatte et al., 2016]) or chemical reactivity of the modification (for pseudouridine [Carlile et al., 2014; Schwartz et al., 2014], m5C [Schaefer, 2015], and 2 0-O-methylation [Dai et al., 2017]).”
Zueva, V. S., Mankin, A. S., BOGDANOV, A. A., & Baratova, L. A. (1985) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1985.tb08704.x · Cited by 59 · see citing works
Lin28 and let-7: roles and regulation in liver diseases
McDaniel, K. M., Hall, C. M., Sato, K., Lairmore, T. C., Marzioni, M., Glaser, S. S., Meng, F., & Alpini, G. D. (2016) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00080.2016 · Cited by 42 · see citing works
An assay for RNA oxidation induced abasic sites using the Aldehyde Reactive Probe
Tanaka, M., Song, H., Küpfer, P. A., Leumann, C. J., & Sonntag, W. E. (2010) · Free Radical Research · doi:10.3109/10715762.2010.535529 · Cited by 38 · see citing works
ChemInform Abstract: Structure and Function of Noncanonical Nucleobases
Carell, T., Brandmayr, C., Hienzsch, A., Mueller, M., Pearson, D., Reiter, V., Thoma, I., Thumbs, P., & Wagner, M. (2012) · ChemInform · doi:10.1002/chin.201247270 · Cited by 34 · cited 1× · see citing works
“…ª 2019 The Autho This is an open access article under the CC BY license (http://creative date, >100 RNA modifications have been identified, which are spread throughout every class of RNA and are evolutionarily conserved throughout all kingdoms of life (Carell et al., 2012; Machnicka et al., 2013).”
BackgroundTranslational halt during elongation caused by G-quadruplex formed by mRNA
Endoh, T., Kawasaki, Y., & Sugimoto, N. (2013) · Methods · doi:10.1016/j.ymeth.2013.05.026 · Cited by 32 · cited 1× · see citing works
“G-quadruplexes and other alternative structures involving non-Watson-Crick base pairing have been described in other classes of RNA, including mRNA (Bugaut and Balasubramanian, 2012); there they are proposed to induce ribosome stalling, thereby inhibiting translation (Endoh et al., 2013).”
BackgroundThe Profile and Dynamics of RNA Modifications in Animals
van Delft, P., Akay, A., Huber, S. M., Bueschl, C., Rudolph, K. L. M., Domenico, T. D., Schuhmacher, R., Miska, E. A., & Balasubramanian, S. (2017) · ChemBioChem · doi:10.1002/cbic.201700093 · Cited by 30 · see citing works
Self-citationGuanine Modification of Inhibitory Oligonucleotides Potentiates Their Suppressive Function
Römmler, F., Jurk, M., Uhlmann, E., Hammel, M., Waldhuber, A., Pfeiffer, L., Wagner, H., Vollmer, J., & Miethke, T. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1300706 · Cited by 24 · see citing works
Flagged first, then by citations
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Sorted by citations
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Barbieri, I., & Kouzarides, T. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-020-0253-2 · Cited by 1,327 · see citing works
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 1,265 · see citing works
Self-citationThe epitranscriptome beyond m6A
Wiener, D., & Schwartz, S. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-020-00295-8 · Cited by 717 · see citing works
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 · see citing works
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Chen, L., & Kim, V. N. (2024) · Cell · doi:10.1016/j.cell.2024.10.024 · Cited by 441 · see citing works
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 · see citing works
“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 423 · see citing works
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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 404 · see citing works
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Delaunay, S., Helm, M., & Frye, M. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-023-00645-2 · Cited by 358 · see citing works
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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 352 · see citing works
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 297 · see citing works
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 304 · see citing works
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 · see citing works
“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 246 · see citing works
“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 239 · see citing works
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 229 · see citing works
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 · see citing works
“…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 221 · see citing works
“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 · see citing works
“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 · see citing works
METTL3 Inhibitors for Epitranscriptomic Modulation of Cellular Processes
Moroz, E., Danzhi Huang, A., Bedi, R. K., Cheriyamkunnel, S. J., Bochenkova, E., Dolbois, A., Rzeczkowski, M. D., Li, Y., Wiedmer, L., & Caflisch, A. (2021) · ChemMedChem · doi:10.1002/cmdc.202100291 · Cited by 200 · see citing works
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 193 · see citing works
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 · see citing works
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 · see citing works
Detection technologies for RNA modifications
Zhang, Y., Lu, L., & Li, X. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00821-0 · Cited by 177 · see citing works
RNA modification: mechanisms and therapeutic targets
Qiu, L., Qian, J., Li, Y., & Han, J. (2023) · Molecular Biomedicine · doi:10.1186/s43556-023-00139-x · Cited by 180 · see citing works
The biogenesis and regulation of animal microRNAs
Kim, H., Lee, Y.-Y., & Kim, V. N. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00805-0 · Cited by 194 · see citing works
“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 182 · see citing works
“157 At present, our understanding of m7G regulators is apparently limited.”
Background1,4,9-Triazaspiro[5.5]undecan-2-one Derivatives as Potent and Selective METTL3 Inhibitors
Dolbois, A., Bedi, R. K., Bochenkova, E., Müller, A., Moroz, E., Danzhi Huang, A., & Caflisch, A. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00773 · Cited by 165 · see citing works
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 · see citing works
Roles of RNA Methylation on Tumor Immunity and Clinical Implications
Zhang, M., Song, J., Yuan, W., Zhang, W., & Sun, Z. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.641507 · Cited by 162 · see citing works
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 · see citing works
“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].”
The role of RNA methylation in tumor immunity and its potential in immunotherapy
Li, Y., Jin, H., Li, Q., Shi, L., Mao, Y., & Zhao, L. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02041-8 · Cited by 156 · see citing works
“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 · see citing works
“m(7)G modifications in tumour suppressor miRNA upregulate the expression of miRNA by promoting the processing and maturation of pri-miRNA, resulting in decreased expression of downstream oncogenes [57, 208].”
BackgroundInfluentialRNA Modifications and Epigenetics in Modulation of Lung Cancer and Pulmonary Diseases
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 139 · see citing works
mRNA Regulation by RNA Modifications
Gilbert, W. V., & Nachtergaele, S. (2023) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-052521-035949 · Cited by 138 · see citing works
“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 · see citing works
Liu, Y., Yang, C., Yong, Z., Chi, Q., Wang, Z., & Sun, B. (2019) · Aging · doi:10.18632/aging.102575 · Cited by 136 · see citing works
“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 · see citing works
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 · see citing works
Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance
Song, J., Yang, P. X., Chen, C., Ding, W., Tillement, O., Bai, H., & Zhang, S. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02266-z · Cited by 145 · see citing works
Human transfer RNA modopathies: diseases caused by aberrations in transfer RNA modifications
Chujo, T., & Tomizawa, K. (2021) · FEBS Journal · doi:10.1111/febs.15736 · Cited by 121 · see citing works
Writers, readers, and erasers RNA modifications and drug resistance in cancer
Chen, D., Gu, X., Nurzat, Y., Xu, L., Li, X., Wu, L., Jiao, H., Gao, P., Zhu, X., Yan, D., et al. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02089-6 · Cited by 126 · see citing works
“This modification involves the addition of a methyl group to the N7 position of ribo-guano-sine [157–160].”
BackgroundMethyltransferase-like proteins in cancer biology and potential therapeutic targeting
Qi, Y., Liu, Z., Hong, L., Li, P., & Ling, Z. (2023) · Journal of Hematology & Oncology · doi:10.1186/s13045-023-01477-7 · Cited by 121 · see citing works
“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].”
BackgroundComputational methods for RNA modification detection from nanopore direct RNA sequencing data
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 116 · see citing works
“…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].”
BackgroundEpigenetic modulations of noncoding RNA: a novel dimension of Cancer biology
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 117 · see citing works
“showed that a subgroup of tumor suppressor miRNAs, including let-7e, contained m7G modification sites [91].”
BackgroundTwo genomes, one cell: Mitochondrial-nuclear coordination via epigenetic pathways
Wiese, M., & Bannister, A. J. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.01.006 · Cited by 116 · see citing works
“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 · see citing works
“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 111 · see citing works
“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 · see citing works
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 · see citing works
“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 · see citing works
“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 100 · see citing works
“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 · see citing works
“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 88 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 77 · see citing works
“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 71 · see citing works
“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., Yao, W., Zhao, Q., Wang, J., Liu, Y., et al. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa504 · Cited by 73 · see citing works
“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 · see citing works
Biological roles of RNA m7G modification and its implications in cancer
Zhang, X., Zhu, W.-Y., Shen, S., Shen, J., & Chen, X.-D. (2023) · Biology Direct · doi:10.1186/s13062-023-00414-5 · Cited by 70 · see citing works
“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 68 · see citing works
Liu, Y., Zhang, Y., Chi, Q., Wang, Z., & Sun, B. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117480 · Cited by 63 · see citing works
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 · see citing works
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 · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works
“…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 · see citing works
“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 59 · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 58 · see citing works
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 · see citing works
Wong, J. M., & Eirin-Lopez, J. M. (2021) · Molecular Biology and Evolution · doi:10.1093/molbev/msab267 · Cited by 57 · see citing works
“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 57 · see citing works
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 · see citing works
“…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 56 · see citing works
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 · see citing works
“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 · see citing works
Jones, A. N., Tikhaia, E., Mourão, A., & Sattler, M. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac080 · Cited by 55 · see citing works
“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 54 · see citing works
“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 · see citing works
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 · see citing works
“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 · see citing works
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 53 · see citing works
“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 · see citing works
“Furthermore, m7G methylation has been known to increase translation efficiency and microRNA processing [44, 45].”
BackgroundZhou, W., Wang, C., Chang, J., Huang, Y.-R., Xue, Q., Miao, C.-G., & Wu, P.-K. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.722728 · Cited by 49 · see citing works
“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 47 · see citing works
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 · see citing works
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 45 · see citing works
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 43 · see citing works
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 · see citing works
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 · see citing works
“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 43 · see citing works
Wang, C., Wang, W., Han, X., Du, L., Li, A., & Huang, G. (2021) · Oncology Letters · doi:10.3892/ol.2021.12591 · Cited by 43 · see citing works
“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
- 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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