{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:00:27Z","timestamp":1791511227542,"version":"4.3.4"},"reference-count":77,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T00:00:00Z","timestamp":1658188800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35NS111631"],"award-info":[{"award-number":["R35NS111631"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01CA186702"],"award-info":[{"award-number":["R01CA186702"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["S10OD030335"],"award-info":[{"award-number":["S10OD030335"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F32CA22104"],"award-info":[{"award-number":["F32CA22104"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001348","name":"Agency for Science, Technology And Research","doi-asserted-by":"crossref","award":["National Science Scholarship"],"award-info":[{"award-number":["National Science Scholarship"]}],"id":[{"id":"10.13039\/501100001348","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"abstract":"<jats:p>\n                    <jats:italic>N<\/jats:italic>\n                    <jats:sup>6<\/jats:sup>\n                    -methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) is a highly prevalent mRNA modification that promotes degradation of transcripts encoding proteins that have roles in cell development, differentiation, and other pathways. METTL3 is the major methyltransferase that catalyzes the formation of m\n                    <jats:sup>6<\/jats:sup>\n                    A in mRNA. As 30% to 80% of m\n                    <jats:sup>6<\/jats:sup>\n                    A can remain in mRNA after METTL3 depletion by CRISPR\/Cas9-based methods, other enzymes are thought to catalyze a sizable fraction of m\n                    <jats:sup>6<\/jats:sup>\n                    A. Here, we reexamined the source of m\n                    <jats:sup>6<\/jats:sup>\n                    A in the mRNA transcriptome. We characterized mouse embryonic stem cell lines that continue to have m\n                    <jats:sup>6<\/jats:sup>\n                    A in their mRNA after\n                    <jats:italic>Mettl3<\/jats:italic>\n                    knockout. We show that these cells express alternatively spliced\n                    <jats:italic>Mettl3<\/jats:italic>\n                    transcript isoforms that bypass the CRISPR\/Cas9 mutations and produce functionally active methyltransferases. We similarly show that other reported\n                    <jats:italic>METTL3<\/jats:italic>\n                    knockout cell lines express altered METTL3 proteins. We find that gene dependency datasets show that most cell lines fail to proliferate after\n                    <jats:italic>METTL3<\/jats:italic>\n                    deletion, suggesting that reported\n                    <jats:italic>METTL3<\/jats:italic>\n                    knockout cell lines express altered METTL3 proteins rather than have full knockout. Finally, we reassessed METTL3\u2019s role in synthesizing m\n                    <jats:sup>6<\/jats:sup>\n                    A using an exon 4 deletion of\n                    <jats:italic>Mettl3<\/jats:italic>\n                    and found that METTL3 is responsible for &gt;95% of m\n                    <jats:sup>6<\/jats:sup>\n                    A in mRNA. Overall, these studies suggest that METTL3 is responsible for the vast majority of m\n                    <jats:sup>6<\/jats:sup>\n                    A in the transcriptome, and that remaining m\n                    <jats:sup>6<\/jats:sup>\n                    A in putative\n                    <jats:italic>METTL3<\/jats:italic>\n                    knockout cell lines is due to the expression of altered but functional METTL3 isoforms.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3001683","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T13:23:11Z","timestamp":1658236991000},"page":"e3001683","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":74,"title":["Alternative splicing of METTL3 explains apparently METTL3-independent m6A modifications in mRNA"],"prefix":"10.1371","volume":"20","author":[{"given":"Hui Xian","family":"Poh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aashiq H.","family":"Mirza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian F.","family":"Pickering","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3615-6958","authenticated-orcid":true,"given":"Samie R.","family":"Jaffrey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,7,19]]},"reference":[{"key":"pbio.3001683.ref001","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0092-8674(74)90153-6","article-title":"Existence of methylated messenger RNA in mouse L cells","volume":"1","author":"RP Perry","year":"1974","journal-title":"Cell"},{"key":"pbio.3001683.ref002","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.1073\/pnas.71.10.3971","article-title":"Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells","volume":"71","author":"R Desrosiers","year":"1974","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pbio.3001683.ref003","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1016\/j.cell.2012.05.003","article-title":"Comprehensive analysis of mrna methylation reveals enrichment in 3\u2019 UTRs and near stop codons","volume":"149","author":"KD Meyer","year":"2012","journal-title":"Cell"},{"key":"pbio.3001683.ref004","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.stem.2014.09.019","article-title":"m6A RNA modification controls cell fate transition in mammalian embryonic stem cells","volume":"15","author":"PJ Batista","year":"2014","journal-title":"Cell Stem Cell"},{"key":"pbio.3001683.ref005","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1126\/science.1261417","article-title":"m6A mRNA methylation facilitates resolution of na\u00efve pluripotency toward differentiation","volume":"347","author":"S Geula","year":"2015","journal-title":"Science"},{"key":"pbio.3001683.ref006","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/ncb2902","article-title":"N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells","volume":"16","author":"Y Wang","year":"2014","journal-title":"Nat Cell Biol"},{"key":"pbio.3001683.ref007","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/nature24678","article-title":"Promoter-bound METTL3 maintains myeloid leukaemia by m6A-dependent translation control","volume":"552","author":"I Barbieri","year":"2017","journal-title":"Nature"},{"key":"pbio.3001683.ref008","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1038\/nm.4416","article-title":"The N6-methyladenosine (m6A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells","volume":"23","author":"LP Vu","year":"2017","journal-title":"Nat Med"},{"issue":"4","key":"pbio.3001683.ref009","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.ccell.2017.03.010","article-title":"Messenger RNA methylation regulates glioblastoma tumorigenesis","volume":"31","author":"D Dixit","year":"2017","journal-title":"Cancer Cell"},{"key":"pbio.3001683.ref010","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/nature21355","article-title":"m6A-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition","volume":"542","author":"BS Zhao","year":"2017","journal-title":"Nature"},{"key":"pbio.3001683.ref011","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.cell.2013.10.026","article-title":"RNA-methylation-dependent RNA processing controls the speed of the circadian clock","volume":"155","author":"JM Fustin","year":"2013","journal-title":"Cell"},{"key":"pbio.3001683.ref012","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/nature15377","article-title":"Dynamic m6A mRNA methylation directs translational control of heat shock response","volume":"526","author":"J Zhou","year":"2015","journal-title":"Nature"},{"key":"pbio.3001683.ref013","doi-asserted-by":"crossref","first-page":"6792","DOI":"10.1038\/ncomms7792","article-title":"FTO influences adipogenesis by regulating mitotic clonal expansion","volume":"6","author":"M Merkestein","year":"2015","journal-title":"Nat Commun"},{"key":"pbio.3001683.ref014","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1038\/cr.2014.151","article-title":"FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis","volume":"24","author":"X Zhao","year":"2014","journal-title":"Cell Res"},{"issue":"7","key":"pbio.3001683.ref015","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.cell.2017.05.045","article-title":"Dynamic RNA modifications in gene expression regulation","volume":"169","author":"IA Roundtree","year":"2017","journal-title":"Cell"},{"key":"pbio.3001683.ref016","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/nrm.2016.132","article-title":"Post-transcriptional gene regulation by mRNA modifications","volume":"18","author":"BS Zhao","year":"2016","journal-title":"Nat Rev Mol Cell Biol"},{"key":"pbio.3001683.ref017","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/s41580-019-0168-5","article-title":"Reading, writing and erasing mRNA methylation","volume":"20","author":"S Zaccara","year":"2019","journal-title":"Nat Rev Mol Cell Biol"},{"key":"pbio.3001683.ref018","first-page":"1233","article-title":"Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase","volume":"3","author":"JA Bokar","year":"1997","journal-title":"RNA"},{"key":"pbio.3001683.ref019","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.molcel.2016.05.041","article-title":"Structural Basis for cooperative function of Mettl3 and Mettl14 methyltransferases","volume":"63","author":"P Wang","year":"2016","journal-title":"Mol Cell"},{"key":"pbio.3001683.ref020","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/nature18298","article-title":"Structural basis of N6-adenosine methylation by the METTL3-METTL14 complex","volume":"534","author":"X Wang","year":"2016","journal-title":"Nature"},{"key":"pbio.3001683.ref021","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nchembio.1432","article-title":"A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation","volume":"10","author":"J Liu","year":"2014","journal-title":"Nat Chem Biol"},{"key":"pbio.3001683.ref022","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.celrep.2014.05.048","article-title":"Perturbation of m6A writers reveals two distinct classes of mRNA methylation at internal and 5\u2019 sites","volume":"8","author":"S Schwartz","year":"2014","journal-title":"Cell Rep"},{"key":"pbio.3001683.ref023","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/nature21671","article-title":"RNA m6A methylation regulates the ultraviolet-induced DNA damage response","volume":"543","author":"Y Xiang","year":"2017","journal-title":"Nature"},{"key":"pbio.3001683.ref024","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/s41589-020-0524-y","article-title":"m6A-binding YTHDF proteins promote stress granule formation","volume":"16","author":"Y Fu","year":"2020","journal-title":"Nat Chem Biol"},{"key":"pbio.3001683.ref025","doi-asserted-by":"crossref","first-page":"6251","DOI":"10.1093\/nar\/gkaa347","article-title":"Dynamic landscape and evolution of m6A methylation in human","volume":"48","author":"H Zhang","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"pbio.3001683.ref026","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.3892\/ol.2020.11794","article-title":"Knockdown of m6A methyltransferase METTL3 in gastric cancer cells results in suppression of cell proliferation","volume":"20","author":"L Jiang","year":"2020","journal-title":"Oncol Lett"},{"key":"pbio.3001683.ref027","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12943-020-01190-w","article-title":"m6A-dependent glycolysis enhances colorectal cancer progression","volume":"19","author":"C Shen","year":"2020","journal-title":"Mol Cancer"},{"key":"pbio.3001683.ref028","doi-asserted-by":"crossref","first-page":"973","DOI":"10.3892\/or.2020.7665","article-title":"m6A methyltransferase METTL3 maintains colon cancer tumorigenicity by suppressing SOCS2 to promote cell proliferation","volume":"44","author":"J Xu","year":"2020","journal-title":"Oncol Rep"},{"key":"pbio.3001683.ref029","doi-asserted-by":"crossref","first-page":"11083","DOI":"10.1093\/nar\/gkaa816","article-title":"METTL3 counteracts premature aging via m6A-dependent stabilization of MIS12 mRNA","volume":"48","author":"Z Wu","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"pbio.3001683.ref030","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/nature23450","article-title":"m6A mRNA methylation controls T cell homeostasis by targeting the IL-7\/STAT5\/SOCS pathways","volume":"548","author":"HB Li","year":"2017","journal-title":"Nature"},{"key":"pbio.3001683.ref031","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1038\/cr.2017.117","article-title":"Mettl3-\/Mettl14-mediated mRNA N 6-methyladenosine modulates murine spermatogenesis","volume":"27","author":"Z Lin","year":"2017","journal-title":"Cell Res"},{"key":"pbio.3001683.ref032","first-page":"28","article-title":"m6A RNA methylation maintains hematopoietic stem cell identity and symmetric commitment","author":"Y Cheng","year":"2019","journal-title":"Cell Rep"},{"key":"pbio.3001683.ref033","doi-asserted-by":"crossref","first-page":"eabd4742","DOI":"10.1126\/sciadv.abd4742","article-title":"Pooled CRISPR screening identifies m6A as a positive regulator of macrophage activation","volume":"7","author":"J Tong","year":"2021","journal-title":"Sci Adv"},{"key":"pbio.3001683.ref034","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1101\/gr.271635.120","article-title":"Acute depletion of METTL3 implicates N6-methyladenosine in alternative intron\/exon inclusion in the nascent transcriptome","volume":"31","author":"G Wei","year":"2021","journal-title":"Genome Res"},{"key":"pbio.3001683.ref035","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/s41556-021-00835-2","article-title":"METTL16 exerts an m6A-independent function to facilitate translation and tumorigenesis","volume":"24","author":"R Su","year":"2022","journal-title":"Nat Cell Biol"},{"key":"pbio.3001683.ref036","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1007\/s13238-018-0518-7","article-title":"Solution structure of the RNA recognition domain of METTL3-METTL14 N6-methyladenosine methyltransferase","volume":"10","author":"J Huang","year":"2019","journal-title":"Protein Cell"},{"key":"pbio.3001683.ref037","article-title":"Selective detection of m6A derived from mRNA using the Phospho-tag m6A assay","author":"AH Mirza","year":"2022","journal-title":"bioRxiv"},{"key":"pbio.3001683.ref038","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1093\/nar\/28.22.e96","article-title":"A simple and reliable 5\u2019-RACE approach","volume":"28","author":"G Schramm","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"pbio.3001683.ref039","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1261\/rna.064063.117","article-title":"Interactions, localization, and phosphorylation of the m6A generating METTL3\u2013METTL14\u2013WTAP complex","volume":"24","author":"E Sch\u00f6ller","year":"2018","journal-title":"RNA"},{"key":"pbio.3001683.ref040","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/s41586-021-03536-w","article-title":"Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia","volume":"593","author":"E Yankova","year":"2021","journal-title":"Nature"},{"key":"pbio.3001683.ref041","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.chom.2017.08.004","article-title":"Epitranscriptomic enhancement of influenza A virus gene expression and replication","volume":"22","author":"DG Courtney","year":"2017","journal-title":"Cell Host Microbe"},{"key":"pbio.3001683.ref042","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1053\/j.gastro.2020.11.013","article-title":"RNA N6-methyladenosine methyltransferase mettl3 facilitates colorectal cancer by activating the m6A-GLUT1-mTORC1 axis and is a therapeutic target","volume":"160","author":"H Chen","year":"2021","journal-title":"Gastroenterology"},{"key":"pbio.3001683.ref043","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1038\/ng.3984","article-title":"Computational correction of copy number effect improves specificity of CRISPR-Cas9 essentiality screens in cancer cells","volume":"49","author":"RM Meyers","year":"2017","journal-title":"Nat Genet"},{"key":"pbio.3001683.ref044","first-page":"720243","article-title":"Extracting biological insights from the project Achilles genome-scale CRISPR screens in cancer cell lines","author":"J Dempster","year":"2019","journal-title":"bioRxiv"},{"key":"pbio.3001683.ref045","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-021-21898-7","article-title":"Integrated cross-study datasets of genetic dependencies in cancer","volume":"12","author":"C Pacini","year":"2021","journal-title":"Nat Commun"},{"key":"pbio.3001683.ref046","article-title":"Chronos: a CRISPR cell population dynamics model","author":"JM Dempster","year":"2021","journal-title":"bioRxiv"},{"key":"pbio.3001683.ref047","unstructured":"DepMap, Broad. DepMap 21Q4 Public. In: figshare [Internet]. 2021 [cited 2021 Nov 15]. https:\/\/figshare.com\/articles\/dataset\/DepMap_21Q4_Public\/16924132\/1."},{"key":"pbio.3001683.ref048","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/cr.2014.3","article-title":"Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase","volume":"24","author":"XL Ping","year":"2014","journal-title":"Cell Res"},{"key":"pbio.3001683.ref049","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-020-03071-y","article-title":"N6-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1\/HK2 modification","volume":"11","author":"Q Wang","year":"2020","journal-title":"Cell Death Dis"},{"key":"pbio.3001683.ref050","doi-asserted-by":"crossref","first-page":"144076","DOI":"10.1016\/j.gene.2019.144076","article-title":"N6-methyladenosine METTL3 promotes the breast cancer progression via targeting Bcl-2","volume":"722","author":"H Wang","year":"2020","journal-title":"Gene"},{"key":"pbio.3001683.ref051","first-page":"1","article-title":"METTL3-mediated N6-methyladenosine modification is critical for epithelial-mesenchymal transition and metastasis of gastric cancer","volume":"18","author":"B Yue","year":"2019","journal-title":"Mol Cancer"},{"issue":"2","key":"pbio.3001683.ref052","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3390\/genes10020141","article-title":"N6-methyladenosine landscape of glioma stem-like cells: METTL3 is essential for the expression of actively transcribed genes and sustenance of the oncogenic signaling","volume":"10","author":"A Visvanathan","year":"2019","journal-title":"Genes"},{"key":"pbio.3001683.ref053","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1126\/science.1225829","article-title":"A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity","volume":"337","author":"M Jinek","year":"2012","journal-title":"Science"},{"key":"pbio.3001683.ref054","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1038\/nprot.2013.143","article-title":"Genome engineering using the CRISPR-Cas9 system","volume":"8","author":"FA Ran","year":"2013","journal-title":"Nat Protoc"},{"key":"pbio.3001683.ref055","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3390\/cells5040045","article-title":"Random splicing of several exons caused by a single base change in the target exon of CRISPR\/Cas9 mediated gene knockout","volume":"5","author":"M Kapahnke","year":"2016","journal-title":"Cell"},{"key":"pbio.3001683.ref056","first-page":"1","article-title":"CRISPR\/Cas9-mediated genome editing induces exon skipping by alternative splicing or exon deletion","volume":"18","author":"H Mou","year":"2017","journal-title":"Genome Biol"},{"key":"pbio.3001683.ref057","doi-asserted-by":"crossref","first-page":"e0178700","DOI":"10.1371\/journal.pone.0178700","article-title":"Frameshift indels introduced by genome editing can lead to in-frame exon skipping","volume":"12","author":"S Lalonde","year":"2017","journal-title":"PLoS ONE"},{"key":"pbio.3001683.ref058","doi-asserted-by":"crossref","first-page":"e1013","DOI":"10.1371\/journal.pone.0001013","article-title":"Variable expression of Cre recombinase transgenes precludes reliable prediction of tissue-specific gene disruption by tail-biopsy genotyping","volume":"2","author":"TJ Schulz","year":"2007","journal-title":"PLoS ONE"},{"key":"pbio.3001683.ref059","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/nature11112","article-title":"Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq","volume":"485","author":"D Dominissini","year":"2012","journal-title":"Nature"},{"key":"pbio.3001683.ref060","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1038\/nmeth.3453","article-title":"Single-nucleotide-resolution mapping of m6A and m6Am throughout the transcriptome","volume":"12","author":"B Linder","year":"2015","journal-title":"Nat Methods"},{"key":"pbio.3001683.ref061","first-page":"1","article-title":"Atlas of quantitative single-base-resolution N6-methyl-adenine methylomes","volume":"10","author":"CWQ Koh","year":"2019","journal-title":"Nat Commun"},{"key":"pbio.3001683.ref062","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1038\/s41592-021-01280-7","article-title":"Systematic calibration of epitranscriptomic maps using a synthetic modification-free RNA library","volume":"18","author":"Z Zhang","year":"2021","journal-title":"Nat Methods"},{"key":"pbio.3001683.ref063","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1016\/j.cell.2013.10.047","article-title":"High-Resolution mapping reveals a conserved, widespread, dynamic mRNA methylation program in yeast meiosis","volume":"155","author":"S Schwartz","year":"2013","journal-title":"Cell"},{"key":"pbio.3001683.ref064","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1101\/gad.301036.117","article-title":"m6A mRNA modifications are deposited in nascent pre-mRNA and are not required for splicing but do specify cytoplasmic turnover","volume":"31","author":"S Ke","year":"2017","journal-title":"Genes Dev"},{"key":"pbio.3001683.ref065","doi-asserted-by":"crossref","first-page":"6590","DOI":"10.1038\/s41598-020-63355-3","article-title":"Limits in the detection of m6A changes using MeRIP\/m6A-seq","volume":"10","author":"ABR McIntyre","year":"2020","journal-title":"Sci Rep"},{"key":"pbio.3001683.ref066","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1261\/rna.041178.113","article-title":"Probing N6-methyladenosine RNA modification status at single nucleotide resolution in mRNA and long noncoding RNA","volume":"19","author":"N Liu","year":"2013","journal-title":"RNA"},{"key":"pbio.3001683.ref067","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.15252\/embr.201744940","article-title":"Human METTL16 is a N6-methyladenosine (m6A) methyltransferase that targets pre-mRNAs and various non-coding RNAs","volume":"18","author":"AS Warda","year":"2017","journal-title":"EMBO Rep"},{"key":"pbio.3001683.ref068","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.cell.2017.05.003","article-title":"The U6 snRNA m6A methyltransferase METTL16 regulates SAM synthetase intron retention","volume":"169","author":"KE Pendleton","year":"2017","journal-title":"Cell"},{"key":"pbio.3001683.ref069","doi-asserted-by":"crossref","first-page":"8901","DOI":"10.1016\/S0021-9258(18)43587-9","article-title":"The nucleotide sequence of nuclear U6 (4.7 S) RNA","volume":"255","author":"P Epstein","year":"1980","journal-title":"J Biol Chem"},{"key":"pbio.3001683.ref070","first-page":"1332","article-title":"The nucleotide sequence of nuclear 4.8S RNA of mouse cells","volume":"95","author":"F Harada","year":"1980","journal-title":"Top Catal"},{"key":"pbio.3001683.ref071","first-page":"71","article-title":"Structural Basis for Regulation of METTL16, an S-Adenosylmethionine Homeostasis Factor Article Structural Basis for Regulation of METTL16, an S-Adenosylmethionine Homeostasis Factor","author":"KA Doxtader","year":"2018","journal-title":"Mol Cell"},{"key":"pbio.3001683.ref072","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1021\/bi00647a024","article-title":"5\u2019-Terminal and Internal Methylated Nucleotide Sequences in Hela Cell mRNA","volume":"15","author":"CM Wei","year":"1976","journal-title":"Biochemistry"},{"key":"pbio.3001683.ref073","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/0022-2836(77)90110-3","article-title":"Comparison of methylated sequences in messenger RNA and heterogeneous nuclear RNA from mouse L cells","volume":"115","author":"U Schibler","year":"1977","journal-title":"J Mol Biol"},{"key":"pbio.3001683.ref074","doi-asserted-by":"crossref","first-page":"7719","DOI":"10.1093\/nar\/gkz619","article-title":"The human 18S rRNA m6A methyltransferase METTL5 is stabilized by TRMT112","volume":"47","author":"N van Tran","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"pbio.3001683.ref075","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41589-018-0184-3","article-title":"N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation","volume":"15","author":"H Ma","year":"2019","journal-title":"Nat Chem Biol"},{"key":"pbio.3001683.ref076","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1093\/nar\/gkz1147","article-title":"The human methyltransferase ZCCHC4 catalyses N6-methyladenosine modification of 28S ribosomal RNA","volume":"48","author":"R Pinto","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"pbio.3001683.ref077","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1105\/tpc.108.058883","article-title":"MTA is an Arabidopsis messenger RNA adenosine methylase and interacts with a homolog of a sex-specific splicing factor","volume":"20","author":"S Zhong","year":"2008","journal-title":"Plant Cell"}],"container-title":["PLOS Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3001683","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T13:24:24Z","timestamp":1658237064000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3001683"}},"subtitle":[],"editor":[{"given":"Wendy V","family":"Gilbert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,7,19]]},"references-count":77,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7,19]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pbio.3001683","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.12.15.472866","asserted-by":"object"}]},"ISSN":["1545-7885"],"issn-type":[{"value":"1545-7885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,19]]}}}