China Animal Husbandry & Veterinary Medicine ›› 2022, Vol. 49 ›› Issue (1): 197-207.doi: 10.16431/j.cnki.1671-7236.2022.01.021
• Genetics and Breeding • Previous Articles Next Articles
SHI Yuanjun, MI Siyuan, YU Ying
Received:2021-09-06
Online:2022-01-05
Published:2021-12-29
CLC Number:
SHI Yuanjun, MI Siyuan, YU Ying. Research Progress on m6A Epigenetic Modification and Its Regulation Mechanism[J]. China Animal Husbandry & Veterinary Medicine, 2022, 49(1): 197-207.
| [1] MAURANO M T,HUMBERT R,RYNES E,et al.Systematic localization of common disease-associated variation in regulatory DNA[J].Science,2012,337(6099):1190-1195. [2] WELTER D,MACARTHUR J,MORALES J,et al.The NHGRI GWAS catalog,a curated resource of SNP-trait associations[J].Nucleic Acids Research,2013,42(D1):D1001-D1006. [3] TRYNKA G,WESTRA H,SLOWIKOWSKI K,et al.Disentangling the effects of colocalizing genomic annotations to functionally prioritize non-coding variants within complex-trait loci[J].The American Journal of Human Genetics,2015,97(1):139-152. [4] BOCCALETTO P,MACHNICKA M A,PURTA E,et al.MODOMICS:A database of RNA modification pathways.2017 update[J].Nucleic Acids Research,2018,46(D1):D303-D307. [5] DOMINISSINI D,NACHTERGAELE S,MOSHITCH-MOSHKOVITZ S,et al.The dynamic N(1)-methyladenosine methylome in eukaryotic messenger RNA[J].Nature,2016,530(7591):441-446. [6] YANG X,YANG Y,SUN B,et al.5-methylcytosine promotes mRNA export——NSUN2 as the methyltransferase and ALYREF as an m5C reader[J].Cell Research,2017,27(5):606-625. [7] ZACCARA S,RIES R J,JAFFREY S R.Reading,writing and erasing mRNA methylation[J].Nature Reviews Molecular Cell Biology,2019,20(10):608-624. [8] DESROSIERS R,FRIDERICI K,ROTTMAN F.Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells[J].Proceedings of the National Academy of Sciences of the United States of America,1974,71(10):3971-3975. [9] DOMINISSINI D,MOSHITCH-MOSHKOVITZ S,SCHWARTZ S,et al.Topology of the human and mouse m6A RNA methylomes revealed by m6A-Seq[J].Nature,2012,485(7397):201-206. [10] MEYER K D,SALETORE Y,ZUMBO P,et al.Comprehensive analysis of mRNA methylation reveals enrichment in 3' UTRs and near stop codons[J].Cell,2012,149(7):1635-1646. [11] ZHANG Z,LUO K,ZOU Z,et al.Genetic analyses support the contribution of mRNA N6-methyladenosine (m6A) modification to human disease heritability[J].Nature Genetics,2020,52(9):939-949. [12] HUANG H,WENG H,CHEN J.The biogenesis and precise control of RNA m6A methylation[J].Trends in Genetics,2020,36(1):44-52. [13] SCHÖLLER E,WEICHMANN F,TREIBER T,et al.Interactions,localization,and phosphorylation of the m6A generating METTL3-METTL14-WTAP complex[J].RNA,2018,24(4):499-512. [14] ŚLEDŹ P,JINEK M.Structural insights into the molecular mechanism of the m6A writer complex[J].eLife,2016,5:e18434. [15] HORIUCHI K,KAWAMURA T,IWANARI H,et al.Identification of Wilms' tumor 1-associating protein complex and its role in alternative splicing and the cell cycle[J].Journal of Biological Chemistry,2013,288(46):33292-33302. [16] FU Y,DOMINISSINI D,RECHAVI G,et al.Gene expression regulation mediated through reversible m6A RNA methylation[J].Nature Reviews Genetics,2014,15(5):293-306. [17] IMAM H,KHAN M,GOKHALE N S,et al.N6 -methyladenosine modification of Hepatitis B virus RNA differentially regulates the viral life cycle[J].Proceedings of the National Academy of Sciences of the United States of America,2018,115(35):8829-8834. [18] DINA C,MEYRE D,GALLINA S,et al.Variation in FTO contributes to childhood obesity and severe adult obesity[J].Nature Genetics,2007,39(6):724-726. [19] GERKEN T,GIRARD C A,TUNG Y C,et al.The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase[J].Science,2007,318(5855):1469-1472. [20] ZHENG G,DAHL J A,NIU Y,et al.ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility[J].Molecular Cell,2013,49(1):18-29. [21] AIK W,SCOTTI J S,CHOI H,et al.Structure of human RNA N6-methyladenine demethylase ALKBH5 provides insights into its mechanisms of nucleic acid recognition and demethylation[J].Nucleic Acids Research,2014,42(7):4741-4754. [22] FU Y,JIA G,PANG X,et al.FTO-mediated formation of N6-hydroxymethyladenosine and N6-formyladenosine in mammalian RNA[J].Nature Communications,2013,4:1798. [23] BARTOSOVIC M,MOLARES H C,GREGOROVA P,et al.N6-methyladenosine demethylase FTO targets pre-mRNAs and regulates alternative splicing and 3'-end processing[J].Nucleic Acids Research,2017,45(19):11356-11370. [24] JIA G,FU Y,ZHAO X,et al.N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO[J].Nature Chemical Biology,2011,7(12):885-887. [25] WANG X,LU Z,GOMEZ A,et al.N6-methyladenosine-dependent regulation of messenger RNA stability[J].Nature,2014,505(7481):117-120. [26] HAN D,LIU J,CHEN C,et al.Anti-tumour immunity controlled through mRNA m6A methylation and YTHDF1 in dendritic cells[J].Nature,2019,566(7743):270-274. [27] SHI H,WEI J,HE C.Where,when,and how:Context-dependent functions of RNA methylation writers,readers,and erasers[J].Molecular Cell,2019,74(4):640-650. [28] MEYER K D,SALETORE Y,ZUMBO P,et al.Comprehensive analysis of mRNA methylation reveals enrichment in 3' UTRs and near stop codons[J].Cell,2012,149(7):1635-1646. [29] CHOE J,LIN S,ZHANG W,et al.mRNA circularization by METTL3-eIF3h enhances translation and promotes oncogenesis[J].Nature,2018,561(7724):556-560. [30] HSU P J,ZHU Y,MA H,et al.YTHDC2 is an N6-methyladenosine binding protein that regulates mammalian spermatogenesis[J].Cell Research,2017,27(9):1115-1127. [31] DU H,ZHAO Y,HE J,et al.YTHDF2 destabilizes m6A-containing RNA through direct recruitment of the CCR4-NOT deadenylasecomplex[J].Nature Communications,2016,7(1):12626. [32] ZHOU J,WAN J,GAO X,et al.Dynamic m(6)A mRNA methylation directs translational control of heat shock response[J].Nature,2015,526(7574):591-594. [33] WAN Y,QU K,ZHANG Q C,et al.Landscape and variation of RNA secondary structure across the human transcriptome[J].Nature,2014,505(7485):706-709. [34] LIU N,DAI Q,ZHENG G,et al.N(6)-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions[J].Nature,2015,518(7540):560-564. [35] NAGARAJAN A,JANOSTIAK R,WAJAPEYEE N.Dot blot analysis for Measuring Global N6-methyladenosine Modification of RNA[M].New York:Springer,2018. [36] KELLNER S,BURHENNE J,HELM M.Detection of RNA modifications[J].RNA Biology,2014,7(2):237-247. [37] ZHANG L,XIONG Q,PEA PEREZ S,et al.ALKBH7-mediated demethylation regulates mitochondrial polycistronic RNA processing[J].Nature Cell Biology,2021,23(7):684-691. [38] LINDER B,GROZHIK A V,OLARERIN-GEORGE A O,et al.Single-nucleotide-resolution mapping of m6A and m6Am throughout the transcriptome[J].Nature Methods,2015,12(8):767-772. [39] LIU N,PARISIEN M,DAI Q,et al.Probing N6-methyladenosine RNA modification status at single nucleotide resolution in mRNA and long noncoding RNA[J].RNA,2013,19(12):1848-1856. [40] XIAO Y,WANG Y,TANG Q,et al.An elongation- and ligation-based qPCR amplification method for the radiolabeling-free detection of locus-specific N6-methyladenosine modification[J].Angewandte Chemie International Edition,2018,57(49):15995-16000. [41] WANG Y,XIAO Y,DONG S,et al.Antibody-free enzyme-assisted chemical approach for detection of N6-methyladenosine[J].Nature Chemical Biology,2020,16(8):896-903. [42] CHEN Y,HAO C,LIU A X,et al.Appearance-consistent video object segmentation based on a multinomial event model[J].ACM Transactions on Multimedia Computing,Communications,and Applications,2019,15(2):1-15. [43] VILFAN I D,TSAI Y C,CLARK T A,et al.Analysis of RNA base modification and structural rearrangement by single-molecule Real-time detection of reverse transcription[J].Journal of Nanobiotechnology,2013,11:8. [44] GARALDE D R,SNELL E A,JACHIMOWICZ D,et al.Highly parallel direct RNA sequencing on an array of nanopores[J].Nature Methods,2018,15(3):201-206. [45] WANG X,WU R,LIU Y,et al.m6A mRNA methylation controls autophagy and adipogenesis by targeting Atg5 and Atg7[J].Autophagy,2020,16(7):1221-1235. [46] HENG J,WU Z,TIAN M,et al.Excessive BCAA regulates fat metabolism partially through the modification of m6A RNA methylation in weanling piglets[J].Nutrition & Metabolism,2020,17(1):10. [47] ZHANG X,YAO Y,HAN J,et al.Longitudinal epitranscriptome profiling reveals the crucial role of N6-methyladenosine methylation in porcine prenatal skeletal muscle development[J].Journal of Genetics and Genomics,2020,47(8):466-476. [48] XI L,CARROLL T,MATOS I,et al.m6A RNA methylation impacts fate choices during skin morphogenesis[J].eLife,2020,9:e56980. [49] WANG Y,ZHENG Y,GUO D,et al.m6A methylation analysis of differentially expressed genes in skin tissues of coarse and fine type liaoningcashmere goats[J].Frontiers in Genetics,2020,10:1318. [50] CHANG Y,BRITO L F,ALVARENGA A B,et al.Incorporating temperament traits in dairy cattle breeding programs:Challenges and opportunities in the phenomicsera[J].Animal Frontiers,2020,10(2):29-36. [51] SHAFIK A M,ZHANG F,GUO Z,et al.N6-methyladenosine dynamics in neurodevelopment and aging,and its potential role in Alzheimer's disease[J].Genome Biology,2021,22(1):17. [52] WU R,LIU Y,ZHAO Y,et al.m6A methylation controls pluripotency of porcine induced pluripotent stem cells by targeting SOCS3/JAK2/STAT3 pathway in a YTHDF1/YTHDF2-orchestrated manner[J].Cell Death & Disease,2019,10(3):171. [53] KIDDER G M,VANDERHYDEN B C.Bidirectional communication between oocytes and follicle cells:Ensuring oocyte developmental competence[J].Canadian Journal of Physiology and Pharmacology,2010,88(4):399-413. [54] CAO Z,ZHANG D,WANG Y,et al.Identification and functional annotation of m6A methylation modification in granulosa cells during antral follicle development in pigs[J].Animal Reproduction Science,2020,219:106510. [55] LU Z,LIU J,YUAN C,et al.m6A mRNA methylation analysis provides novel insights into heat stress responses in the liver tissue of sheep[J].Genomics,2021,113(1):484-492. [56] YU J,LI Y,WANG T,et al.Modification of N6-methyladenosine RNA methylation on heat shock protein expression[J].PLoS One,2018,13(6):e198604. [57] LU Z,MA Y,LI Q,et al.The role of N6-methyladenosine RNA methylation in the heat stress response of sheep (Ovis aries)[J].Cell Stress and Chaperones,2019,24(2):333-342. [58] HENG J,TIAN M,ZHANG W,et al.Maternal heat stress regulates the early fat deposition partly through modification of m6A RNA methylation in neonatal piglets[J].Cell Stress and Chaperones,2019,24(3):635-645. [59] KISLIOUK T,ROSENBERG T,BEN-NUN O,et al.Early-life m6A RNA demethylation by fat mass and obesity-associated protein (FTO) influences resilience or vulnerability to heat stress later in life[J].eNeuro,2020,7(3):519-549. [60] WETMORE C,OLSON L,BEAN A J.Regulation of brain-derived neurotrophic factor (BDNF) expression and release from hippocampal neurons is mediated by non-NMDA type glutamate receptors[J].The Journal of Neuroscience,1994,14(3):1688-1700. [61] ALDERSON R F,ALTERMAN A L,BARDE Y A,et al.Brain-derived neurotrophic factor increases survival and differentiated functions of rat septal cholinergic neurons in culture[J].Neuron,1990,5(3):297-306. [62] BOHLEN UND H O,MINICHIELLO L,UNSICKER K.Haploinsufficiency for trkB and trkC receptors induces cell loss and accumulation of alpha-synuclein in the substantia nigra[J].The FASEB Journal,2005,19(12):1740-1742. [63] MCFADDEN M J,MCINTYRE A B R,MOURELATOS H,et al.Post-transcriptional regulation of antiviral gene expression by N6-methyladenosine[J].Cell Reports,2021,34(9):108798. [64] QIU W,ZHANG Q,ZHANG R,et al.N6-methyladenosine RNA modification suppresses antiviral innate sensing pathways via reshaping double-stranded RNA[J].Nature Communications,2021,12(1):1582. [65] WANG L,WEN M,CAO X.Nuclear hnRNPA2B1 initiates and amplifies the innate immune response to DNA viruses[J].Science,2019,365(6454):v758. [66] CHEN J,JIN L,WANG Z,et al.N6-methyladenosine regulates PEDV replication and host gene expression[J].Virology,2020,548:59-72. [67] LI N,HUI H,BRAY B,et al.METTL3 regulates viral m6A RNA modification and host cell innate immune responses during SARS-CoV-2 infection[J].Cell Reports,2021,35(6):109091. [68] HU J,LIN Y.Fusarium infection alters the m6A-modified transcript landscape in the cornea[J].Experimental Eye Research,2020,200:108216. [69] ZONG X,WANG H,XIAO X,et al.Enterotoxigenic Escherichia coli infection promotes enteric defensin expression via FOXO6-METTL3-m6A-GPR161 signalling axis[J].RNA Biology,2021,18(4):576-586. [70] HUANG H,WENG H,CHEN J.m6A modification in coding and non-coding RNAs:Roles and therapeutic implications in cancer[J].Cancer Cell,2020,37(3):270-288. [71] LI Z,WENG H,SU R,et al.FTO plays an oncogenic role in acute myeloid leukemia as a N6-methyladenosine RNA demethylase[J].Cancer cell,2017,31(1):127-141. [72] SU R,DONG L,LI Y,et al.Targeting FTO suppresses cancer stem cell maintenance and immune evasion[J].Cancer Cell,2020,38(1):79-96. [73] YANKOVA E,BLACKABY W,ALBERTELLA M,et al.Small molecule inhibition of METTL3 as a strategy against myeloid leukaemia[J].Nature,2021,593(7860):597-601. [74] RAHAYU A P,HARTATIK T,PURNOMOADI A,et al.Association of single nucleotide polymorphisms in the fatty acid synthase,LOC514211,and fat mass and obesity-associated genes with milk traits in Indonesian-Holstein dairy cattle[J].Veterinary World,2019,12(7):1160-1166. [75] XIANG R,VAN DEN BERG I,MACLEOD I M,et al.Effect direction meta-analysis of GWAS identifies extreme,prevalent and shared pleiotropy in a large mammal[J].Communications Biology,2020,3(1):88. [76] IBEAGHA-AWEMU E M,PETERS S O,AKWANJI K A,et al.High density genome wide genotyping-by-sequencing and association identifies common and low frequency SNPs,and novel candidate genes influencing cow milk traits[J].Scientific Reports,2016,6(1):31109. [77] WANG S,LIU S,YUAN T,et al.Genetic effects of FTO gene insertion/deletion (InDel) on fat-tail measurements and growth traits in Tong sheep[J].Animal Biotechnology,2021,32(2):229-239. [78] WANG H,ZHANG L,CAO J,et al.Genome-wide specific selection in three domestic sheep breeds[J].PLoS One,2015,10(6):e128688. [79] SEBERT S P,HYATT M A,CHAN L L,et al.Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression[J].Reproduction,2010,139(1):265-274. [80] FAN Y,ZHANG C,ZHU G.Profiling of RNA N6-methyladenosine methylation during follicle selection in chicken ovary[J].Poultry Science,2019,98(11):6117-6124. [81] HU Y,FENG Y,ZHANG L,et al.GR-mediated FTO transactivation induces lipid accumulation in hepatocytes via demethylation of m6A on lipogenic mRNAs[J].RNA Biology,2020,17(7):930-942. [82] HUANG H,LIU L,LI C,et al.Fat mass- and obesity-associated (FTO) gene promoted myoblast differentiation through the focal adhesion pathway in chicken[J].3 Biotech,2020,10(9):403. [83] SONG C,SONG W T,SHU J T,et al.Tissue-and breed-specific expression of the chicken fat mass- and obesity-associated gene (FTO)[J].Genetics and Molecular Research,2015,14(3):10500-10506. [84] MATHIYALAGAN P,ADAMIAK M,MAYOURIAN J,et al.FTO-dependent N6-methyladenosine regulates cardiac function during remodeling and repair[J].Circulation,2019,139(4):518-532. [85] WANG Y,YU X,LIU Y,et al.Reduced nucleic acid methylation impairs meiotic maturation and developmental potency of pig oocytes[J].Theriogenology,2018,121:160-167. [86] FU Y,LI L,REN S.Effect of FTO expression and polymorphism on fat deposition in Suzhong pigs[J].Asian-Australasian Journal of Animal Sciences,2013,26(10):1365-1373. [87] HOU G,ZHAO X,LI L,et al.SUMOylation of YTHDF2 promotes mRNA degradation and cancer progression by increasing its binding affinity with m6A-modified mRNAs[J].Nucleic Acids Research,2021,49(5):2859-2877. [88] YU F,WEI J,CUI X,et al.Post-translational modification of RNA m6A demethylase ALKBH5 regulates ROS-induced DNA damage response[J].Nucleic Acids Research,2021,49(10):5779-5797. [89] ALARCÓN C R,GOODARZI H,LEE H,et al.HNRNPA2B1 is a mediator of m6A-dependent nuclear RNA processing events[J].Cell,2015,162(6):1299-1308. [90] HUANG H,WENG H,ZHOU K,et al.Histone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally[J].Nature,2019,567(7748):414-419. [91] WU C,CHEN W,HE J,et al.Interplay of m6A and H3K27 trimethylation restrains inflammation during bacterial infection[J].Science Advances,2020,6(34):a647. |
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