2021
m6A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity
Qin Y, Li B, Arumugam S, Lu Q, Mankash SM, Li J, Sun B, Li J, Flavell RA, Li HB, Ouyang X. m6A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity. Cell Reports 2021, 37: 109968. PMID: 34758326, PMCID: PMC8667589, DOI: 10.1016/j.celrep.2021.109968.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseProgression of NAFLDLineage-restricted deletionFatty liver diseaseMultiple mRNA transcriptsMyeloid cell activationDiet-induced developmentMethyladenosine (m<sup>6</sup>A) RNA modificationMRNA metabolismProtein methyltransferaseLiver diseaseRNA modificationsCellular stressMetabolic reprogrammingDDIT4 mRNACell activationObesityDifferential expressionMammalian targetMRNA transcriptsSignificant downregulationCytokine stimulationPathway activityMetabolic phenotypeMRNA levelsMETTL3-mediated m6A RNA methylation promotes the anti-tumour immunity of natural killer cells
Song H, Song J, Cheng M, Zheng M, Wang T, Tian S, Flavell RA, Zhu S, Li HB, Ding C, Wei H, Sun R, Peng H, Tian Z. METTL3-mediated m6A RNA methylation promotes the anti-tumour immunity of natural killer cells. Nature Communications 2021, 12: 5522. PMID: 34535671, PMCID: PMC8448775, DOI: 10.1038/s41467-021-25803-0.Peer-Reviewed Original ResearchMeSH KeywordsAdenosineAnimalsCarcinogenesisCell Line, TumorGene DeletionHomeostasisInterleukin-15Killer Cells, NaturalLymphocytes, Tumor-InfiltratingMethylationMethyltransferasesMice, Inbred C57BLMice, KnockoutNeoplasmsProtein Tyrosine Phosphatase, Non-Receptor Type 11Proto-Oncogene Proteins c-aktRNASignal TransductionTumor MicroenvironmentConceptsAnti-tumor immunityNK cellsTumor-infiltrating NK cellsNK cell infiltrationNatural killer cellsAccelerated tumor developmentExert critical rolesImmunosurveillance functionKiller cellsIL-15Cell infiltrationTumor microenvironmentTumor developmentProtein expressionSuppressed activationM6A RNA methylationEffector moleculesExpression levelsMETTL3Cells altersImmunityM6A methylationCellsPositive correlationHomeostasisPooled CRISPR screening identifies m6A as a positive regulator of macrophage activation
Tong J, Wang X, Liu Y, Ren X, Wang A, Chen Z, Yao J, Mao K, Liu T, Meng FL, Pan W, Zou Q, Liu J, Zhou Y, Xia Q, Flavell RA, Zhu S, Li HB. Pooled CRISPR screening identifies m6A as a positive regulator of macrophage activation. Science Advances 2021, 7: eabd4742. PMID: 33910903, PMCID: PMC8081357, DOI: 10.1126/sciadv.abd4742.Peer-Reviewed Original ResearchConceptsMacrophage activationPotential cancer immunotherapy targetInnate immune cellsFaster tumor growthTNF-α productionInnate immune responseCancer immunotherapy targetCre miceImmune cellsImmunotherapy targetImmune responseLPS stimulationTumor growthBacterial infectionsTop candidate genesDeficient macrophagesMultiple cellular responsesMETTL3 deficiencyActivationUnknown roleMETTL3Negative regulatorBinding proteinCellular responsesRNA binding protein
2020
m6A Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development
Gao Y, Vasic R, Song Y, Teng R, Liu C, Gbyli R, Biancon G, Nelakanti R, Lobben K, Kudo E, Liu W, Ardasheva A, Fu X, Wang X, Joshi P, Lee V, Dura B, Viero G, Iwasaki A, Fan R, Xiao A, Flavell RA, Li HB, Tebaldi T, Halene S. m6A Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development. Immunity 2020, 52: 1007-1021.e8. PMID: 32497523, PMCID: PMC7408742, DOI: 10.1016/j.immuni.2020.05.003.Peer-Reviewed Original ResearchConceptsDouble-stranded RNADeleterious innate immune responseMammalian hematopoietic developmentEndogenous double-stranded RNAHematopoietic developmentInnate immune responseAbundant RNA modificationMurine fetal liverPattern recognition receptor pathwaysImmune responseProtein codingDsRNA formationRNA modificationsWriter METTL3Hematopoietic defectsPerinatal lethalityNative stateConditional deletionAberrant innate immune responsesLoss of METTL3Hematopoietic failureReceptor pathwayAberrant immune responsePrevents formationFetal liver
2018
RNA m6A modification and its function in diseases
Tong J, Flavell RA, Li HB. RNA m6A modification and its function in diseases. Frontiers Of Medicine 2018, 12: 481-489. PMID: 30097961, DOI: 10.1007/s11684-018-0654-8.Peer-Reviewed Original ResearchConceptsM6A modificationPost-transcriptional RNA modificationsRegulation of m6ACore catalytic componentFunction of m6ARNA m6A modificationRNA metabolismRegulatory networksRNA modificationsPhysiological contextHuman diseasesPhysiological roleM6ACatalytic componentFunctional relevanceCell linesM6A modulatorsDifferent cellsDisease conditionsTranscriptomeRecent advancesErasersRegulatorBindsModificationm6A mRNA methylation sustains Treg suppressive functions
Tong J, Cao G, Zhang T, Sefik E, Amezcua Vesely MC, Broughton JP, Zhu S, Li H, Li B, Chen L, Chang HY, Su B, Flavell RA, Li HB. m6A mRNA methylation sustains Treg suppressive functions. Cell Research 2018, 28: 253-256. PMID: 29303144, PMCID: PMC5799823, DOI: 10.1038/cr.2018.7.Peer-Reviewed Original Research
2017
m6A mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways
Li HB, Tong J, Zhu S, Batista PJ, Duffy EE, Zhao J, Bailis W, Cao G, Kroehling L, Chen Y, Wang G, Broughton JP, Chen YG, Kluger Y, Simon MD, Chang HY, Yin Z, Flavell RA. m6A mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways. Nature 2017, 548: 338-342. PMID: 28792938, PMCID: PMC5729908, DOI: 10.1038/nature23450.Peer-Reviewed Original ResearchMeSH KeywordsAdenosineAdoptive TransferAnimalsCell DifferentiationCell ProliferationColitisDisease Models, AnimalDNA-Binding ProteinsFemaleHomeostasisInterleukin-7MaleMethylationMethyltransferasesMiceRNA StabilityRNA, MessengerSignal TransductionSTAT5 Transcription FactorSuppressor of Cytokine Signaling 1 ProteinSuppressor of Cytokine Signaling 3 ProteinSuppressor of Cytokine Signaling ProteinsT-Lymphocytes
2016
Recent advances in dynamic m6A RNA modification
Cao G, Li HB, Yin Z, Flavell RA. Recent advances in dynamic m6A RNA modification. Open Biology 2016, 6: 160003. PMID: 27249342, PMCID: PMC4852458, DOI: 10.1098/rsob.160003.Peer-Reviewed Original ResearchConceptsRNA modificationsHigh-throughput sequencing analysisRNA epigenetic modificationM6A RNA modificationRNA splicingEpigenetic modificationsBiological functionsSequencing analysisTranscriptomeRecent advancesDynamic regulation processRegulation processesFundamental rolePossible roleDemethylasesRelated diseasesSplicingMammalsErasersImmune responseRegulationModificationRoleCytogeneticsTypical features