Region-specific RNA m6A methylation represents a new layer of control in the gene regulatory network in the mouse brain

Open Biology

Volumn 7, Issue 9, 2017, Pages

  Chang, Mengqi ^a   Lv, Hongyi ^b,c   Zhang, Weilong ^d   Ma, Chunhui ^a   He, Xue ^a   Zhao, Shunli ^a   Zhang, Zhi Wei ^a   Zeng, Yi Xin ^d   Song, Shuhui ^b   Niu, Yamei ^a   Tong, Wei Min ^a  

^a INSTITUTE OF BASIC MEDICAL SCIENCES   (China)

^b Chinese Academy of Sciences and China National Center for Bioinformation   (China)

^c UNIVERSITY OF CHINESE ACADEMY OF SCIENCES   (China)

^d CANCER HOSPITAL   (China)

Author keywords

epitranscriptomic mark; mouse cerebellum; mouse cerebral cortex; N6 methyladenosine; RNA methylation

Indexed keywords

ADENOSINE; FMR1 PROTEIN, MOUSE; FRAGILE X MENTAL RETARDATION PROTEIN; MESSENGER RNA; N(6)-METHYLADENOSINE;

ANALOGS AND DERIVATIVES; ANIMAL; ANTIBODY SPECIFICITY; BRAIN CORTEX; CEREBELLUM; CYTOLOGY; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE ONTOLOGY; GENE REGULATORY NETWORK; GENETICS; MALE; METABOLISM; METHYLATION; MOLECULAR GENETICS; MOUSE; NERVE CELL; SIGNAL TRANSDUCTION; SYNAPSE;

ADENOSINE; ANIMALS; CEREBELLUM; CEREBRAL CORTEX; FEMALE; FRAGILE X MENTAL RETARDATION PROTEIN; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE ONTOLOGY; GENE REGULATORY NETWORKS; MALE; METHYLATION; MICE; MOLECULAR SEQUENCE ANNOTATION; NEURONS; ORGAN SPECIFICITY; RNA, MESSENGER; SIGNAL TRANSDUCTION; SYNAPSES;

EID: 85044572641     PISSN: None     EISSN: 20462441     Source Type: Journal    
DOI: 10.1098/rsob.170166     Document Type: Article

References (92)

1. 6-methyladenosine-dependent RNA structural switches regulate RNA–protein interactions. Nature 518, 560–564. (doi:10.1038/nature14234)
2. Niu Y, Zhao X, Wu YS, Li MM, Wang XJ, Yang YG. 2013 N6-methyl-adenosine (m6A) in RNA: an old modification with a novel epigenetic function. Genomics Proteomics Bioinform. 11, 8–17. (doi:10. 1016/j.gpb.2012.12.002)
3. Fu Y, Dominissini D, Rechavi G, He C. 2014 Gene expression regulation mediated through reversible m(6)A RNA methylation. Nat. Rev. Genet. 15, 293–306. (doi:10.1038/nrg3724)
4. Xiao W et al. 2016 Nuclear m(6)A reader YTHDC1 regulates mRNA splicing. Mol. Cell. 61, 507–519. (doi:10.1016/j.molcel.2016.01.012)
5. 6A reader YTHDC1 regulates mRNA splicing. Trends Genet. 32, 320–321. (doi:10.1016/j.tig.2016.03.006)
6. Zheng G et al. 2013 ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol. Cell. 49, 18–29. (doi:10.1016/ j.molcel.2012.10.015)
7. Alarcon CR, Lee H, Goodarzi H, Halberg N, Tavazoie SF. 2015 N6-methyladenosine marks primary microRNAs for processing. Nature 519, 482–485. (doi:10.1038/nature14281)
8. 6A-dependent nuclear RNA processing events. Cell 162, 1299–1308. (doi:10.1016/j.cell. 2015.08.011)
9. Choi J et al. 2016 N(6)-methyladenosine in mRNA disrupts tRNA selection and translation-elongation dynamics. Nat. Struct. Mol. Biol. 23, 110–115. (doi:10.1038/nsmb.3148)
10. 6A mRNA methylation directs translational control of heat shock response. Nature 526, 591–594. (doi:10.1038/ nature15377)
11. 6-methyladenosine modulates messenger RNA translation efficiency. Cell 161, 1388–1399. (doi:10.1016/j.cell.2015. 05.014)
12. 6A promotes cap-independent translation. Cell 163, 999–1010. (doi:10.1016/j.cell. 2015.10.012)
13. 6-methyladenosine-modified RNA. Cell Res. 27, 315–328. (doi:10.1038/cr.2017.15)
14. Li A et al. 2017 Cytoplasmic m6A reader YTHDF3 promotes mRNA translation. Cell Res. 27, 444–447. (doi:10.1038/cr.2017.10)
15. Slobodin B, Han R, Calderone V, Vrielink JA, Loayza-Puch F, Elkon R, Agami R. 2017 Transcription impacts the efficiency of mRNA translation via co-transcriptional N6-adenosine methylation. Cell 169, 326–337. (doi:10.1016/j.cell.2017.03.031)
16. Wang X et al. 2014 N6-methyladenosine-dependent regulation of messenger RNA stability. Nature 505, 117–120. (doi:10.1038/nature12730)
17. 6A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex. Nat. Commun. 7, 12626. (doi:10.1038/ncomms12626)
18. Liu N, Pan T. 2016 N6-methyladenosine-encoded epitranscriptomics. Nat. Struct. Mol. Biol. 23, 98–102. (doi:10.1038/nsmb.3162)
19. Patil DP, Chen CK, Pickering BF, Chow A, Jackson C, Guttman M, Jaffrey SR. 2016 m6A RNA methylation promotes XIST-mediated transcriptional repression. Nature 537, 369–373. (doi:10.1038/nature19342)
20. Shah JC, Clancy MJ. 1992 IME4, a gene that mediates MAT and nutritional control of meiosis in Saccharomyces cerevisiae. Mol. Cell Biol. 12, 1078–1086. (doi:10.1128/MCB.12.3.1078)
21. Zhong S, Li H, Bodi Z, Button J, Vespa L, Herzog M, Fray RG. 2008 MTA is an Arabidopsis messenger RNA adenosine methylase and interacts with a homolog of a sex-specific splicing factor. Plant Cell 20, 1278–1288. (doi:10.1105/tpc.108.058883)
22. Ping XL et al. 2014 Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res. 24, 177–189. (doi:10. 1038/cr.2014.3)
23. Hongay CF, Orr-Weaver TL. 2011 Drosophila inducer of Meiosis 4 (IME4) is required for Notch signaling during oogenesis. Proc. Natl Acad. Sci. USA 108, 14 855–14 860. (doi:10.1073/pnas.1111577108)
24. 6-adenosine methylation. Nat. Chem. Biol. 10, 93–95. (doi:10. 1038/nchembio.1432)
25. 6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nat. Cell Biol. 16, 191–198. (doi:10. 1038/ncb2902)
26. 6A mRNA methylation and gene transcription by ZFP217 regulates pluripotency and reprogramming. Cell Stem Cell 17, 689–704. (doi:10.1016/j.stem.2015. 09.005)
27. 6A RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency. Cell Stem Cell 16, 289–301. (doi:10.1016/j.stem.2015.01.016)
28. Geula S et al. 2015 Stem cells. m6A mRNA methylation facilitates resolution of naive pluripotency toward differentiation. Science 347, 1002–1006. (doi:10.1126/science.1261417)
29. 6A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell 15, 707–719. (doi:10.1016/j.stem.2014.09.019)
30. Fustin JM et al. 2013 RNA-methylation-dependent RNA processing controls the speed of the circadian clock. Cell 155, 793–806. (doi:10.1016/j.cell.2013. 10.026)
31. 6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat. Chem. Biol. 7, 885–887. (doi:10.1038/ nchembio.687)
32. Zhao X et al. 2014 FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis. Cell Res. 24, 1403–1419. (doi:10.1038/cr.2014.151)
33. Hess ME et al. 2013 The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry. Nat. Neurosci. 16, 1042–1048. (doi:10.1038/nn.3449)
34. 6-methyladenosine in the prefrontal cortex is associated with memory processes in mice. J. Neurosci. 36, 6771–6777. (doi:10.1523/JNEUROSCI.4053-15.2016)
35. Li L et al. 2017 Fat mass and obesity-associated (FTO) protein regulates adult neurogenesis. Hum. Mol. Genet. 26, 2398–2411. (doi:10.1093/hmg/ ddx128)
36. Yao B, Christian KM, He C, Jin P, Ming GL, Song H. 2016 Epigenetic mechanisms in neurogenesis. Nat. Rev. Neurosci. 17, 537–549. (doi:10.1038/nrn.2016. 70)
37. Guo JU et al. 2011 Neuronal activity modifies the DNA methylation landscape in the adult brain. Nat. Neurosci. 14, 1345–1351. (doi:10.1038/nn. 2900)
38. Hirabayashi Y, Suzki N, Tsuboi M, Endo TA, Toyoda T, Shinga J, Koseki H, Vidal M, Gotoh Y. 2009 Polycomb limits the neurogenic competence of neural precursor cells to promote astrogenic fate transition. Neuron 63, 600–613. (doi:10.1016/j. neuron.2009.08.021)
39. Lim DA, Huang Y-C, Swigut T, Mirick AL, Garcia-Verdugo JM, Wysocka J, Ernst P, Alvarez-Buylla A. 2009 Chromatin remodelling factor Mll1 is essential for neurogenesis from postnatal neural stem cells. Nature 458, 529–533. (doi:10.1038/ nature07726)
40. Ramos AD, Diaz A, Nellore A, Delgado RN, Park KY, Gonzales-Roybal G, Oldham MC, Song JS, Lim DA. 2013 Integration of genome-wide approaches identifies lncRNAs of adult neural stem cells and their progeny in vivo. Cell Stem Cell 12, 616–628. (doi:10.1016/j.stem.2013.03.003)
41. Roundtree IA, He C. 2016 RNA epigenetics—chemical messages for posttranscriptional gene regulation. Curr. Opin. Chem. Biol. 30, 46–51. (doi:10.1016/j.cbpa.2015.10.024)
42. Squires JE, Patel HR, Nousch M, Sibbritt T, Humphreys DT, Parker BJ, Suter CM, Preiss T. 2012 Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA. Nucleic Acids Res. 40, 5023–5033. (doi:10.1093/nar/gks144)
43. 1-methyladenosine methylome in eukaryotic messenger RNA. Nature 530, 441–446. (doi:10. 1038/nature16998)
44. Liu J, Jia G. 2014 Methylation modifications in eukaryotic messenger RNA. J. Genet. Genomics. 41, 21–33. (doi:10.1016/j.jgg.2013.10.002)
45. 1-methyladenosine methylome. Nat. Chem. Biol. 12, 311–316. (doi:10. 1038/nchembio.2040)
46. Nainar S, Marshall PR, Tyler CR, Spitale RC, Bredy TW. 2016 Evolving insights into RNA modifications and their functional diversity in the brain. Nat. Neurosci. 19, 1292–1298. (doi:10.1038/nn.4378)
47. Zhang S et al. 2017 m6A demethylase ALKBH5 maintains tumorigenicity of glioblastoma stem-like cells by sustaining FOXM1 expression and cell proliferation program. Cancer Cell 31, 591–606. (doi:10.1016/j.ccell.2017.02.013)
48. Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR. 2012 Comprehensive analysis of mRNA methylation reveals enrichment in 3’ UTRs and near stop codons. Cell 149, 1635–1646. (doi:10.1016/j.cell.2012.05.003)
49. LoVerso PR, Cui F. 2016 Cell type-specific transcriptome profiling in mammalian brains. Front. Biosci. 21, 973–985. (doi:10.2741/4434)
50. Kessler NJ, Van Baak TE, Baker MS, Laritsky E, Coarfa C, Waterland RA. 2016 CpG methylation differences between neurons and glia are highly conserved from mouse to human. Hum. Mol. Genet. 25, 223–232. (doi:10.1093/hmg/ddv459)
51. Spijker S. 2011 Dissection of rodent brain regions. In Neuroproteomics (ed. KW Li), pp. 13–26. New York, NY: Humana Press.
52. Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL. 2013 TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 14, R36. (doi:10.1186/gb-2013-14-4-r36)
53. Trapnell C, Pachter L, Salzberg SL. 2009 TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25, 1105–1111. (doi:10.1093/ bioinformatics/btp120)
54. Trapnell C et al. 2012 Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat. Protoc. 7, 562–578. (doi:10.1038/nprot.2012.016)
55. Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G, van Baren MJ, Salzberg SL, Wold BJ, Pachter L. 2010 Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat. Biotechnol. 28, 511–515. (doi:10.1038/nbt.1621)
56. Meng J, Cui X, Rao MK, Chen Y, Huang Y. 2013 Exome-based analysis for RNA epigenome sequencing data. Bioinformatics 29, 1565–1567. (doi:10.1093/bioinformatics/btt171)
57. Liu L, Zhang SW, Zhang YC, Liu H, Zhang L, Chen R, Huang Y, Meng J. 2015 Decomposition of RNA methylome reveals co-methylation patterns induced by latent enzymatic regulators of the epitranscriptome. Mol. BioSyst. 11, 262–274. (doi:10.1039/c4mb00604f)
58. Quinlan AR, Hall IM. 2010 BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842. (doi:10.1093/ bioinformatics/btq033)
59. Heinz S et al. 2010 Simple combinations of lineage-determining transcription factors prime cisregulatory elements required for macrophage and B cell identities. Mol. Cell. 38, 576–589. (doi:10. 1016/j.molcel.2010.05.004)
60. Zhang Y et al. 2008 Model-based analysis of ChIP-Seq (MACS). Genome Biol. 9, R137. (doi:10.1186/gb-2008-9-9-r137)
61. 6A-seqbasedon immunocapturing and massively parallel sequencing. Nat. Protoc. 8, 176–189. (doi:10.1038/nprot.2012. 148)
62. Dominissini D et al. 2012 Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 485, 201–206. (doi:10.1038/ nature11112)
63. Huang da W, Sherman BT, Lempicki RA. 2009 Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44–57. (doi:10.1038/nprot.2008.211)
64. Mauer J et al. 2017 Reversible methylation of m6Am in the 5’ cap controls mRNA stability. Nature 541, 371–375. (doi:10.1038/nature21022)
65. 6A epitranscriptome. Nat. Methods 13, 692. (doi:10.1038/nmeth.3898)
66. Linder B, Grozhik AV, Olarerin-George AO, Meydan C, Mason CE, Jaffrey SR. 2015 Single-nucleotide-resolution mapping of m6A and m6Am throughout the transcriptome. Nat. Methods 12, 767–772. (doi:10.1038/nmeth.3453)
67. Cahoy JD et al. 2008 A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J. Neurosci. 28, 264–278. (doi:10.1523/ JNEUROSCI.4178-07.2008)
68. Mellen M, Ayata P, Dewell S, Kriaucionis S, Heintz N. 2012 MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system. Cell 151, 1417–1430. (doi:10. 1016/j.cell.2012.11.022)
69. Croning MD, Marshall MC, McLaren P, Armstrong JD, Grant SG. 2009 G2Cdb: the Genes to Cognition database. Nucleic Acids Res. 37, D846–D851. (doi:10.1093/nar/gkn700)
70. Weingarten J et al. 2014 The proteome of the presynaptic active zone from mouse brain. Mol. Cell Neurosci. 59, 106–118. (doi:10.1016/j.mcn.2014. 02.003)
71. Iacoangeli A, Tiedge H. 2013 Translational control at the synapse: role of RNA regulators. Trends Biochem. Sci. 38, 47–55. (doi:10.1016/j.tibs.2012.11.001)
72. Buffington SA, Huang W, Costa-Mattioli M. 2014 Translational control in synaptic plasticity and cognitive dysfunction. Annu. Rev. Neurosci. 37, 17–38. (doi:10.1146/annurev-neuro-071013-014100)
73. Verkerk AJ et al. 1991 Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65, 905–914. (doi:10. 1016/0092-8674(91)90397-H)
74. Suhl JA, Chopra P, Anderson BR, Bassell GJ, Warren ST. 2014 Analysis of FMRP mRNA target datasets reveals highly associated mRNAs mediated by G-quadruplex structures formed via clustered WGGA sequences. Hum. Mol. Genet. 23, 5479–5491. (doi:10.1093/hmg/ddu272)
75. Anderson BR, Chopra P, Suhl JA, Warren ST, Bassell GJ. 2016 Identification of consensus binding sites clarifies FMRP binding determinants. Nucleic Acids Res. 44, 6649–6659. (doi:10.1093/nar/gkw593)
76. Darnell JC et al. 2011 FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 146, 247–261. (doi:10.1016/j.cell. 2011.06.013)
77. Frank CL et al. 2015 Regulation of chromatin accessibility and Zic binding at enhancers in the developing cerebellum. Nat. Neurosci. 18, 647–656. (doi:10.1038/nn.3995)
78. Szulwach KE et al. 2011 5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging. Nat. Neurosci. 14, 1607–1616. (doi:10.1038/ nn.2959)
79. Chou SJ, Wang C, Sintupisut N, Niou ZX, Lin CH, Li KC, Yeang CH. 2016 Analysis of spatial-temporal gene expression patterns reveals dynamics and regionalization in developing mouse brain. Sci. Rep. 6, 19274. (doi:10.1038/srep19274)
80. Emery B, Barres BA. 2008 Unlocking CNS cell type heterogeneity. Cell 135, 596–598. (doi:10.1016/j. cell.2008.10.031)
81. 6-methyladenosine profiling of rice callus and leaf reveals the presence of tissue-specific competitors involved in selective mRNA modification. RNA Biol. 11, 1180–1188. (doi:10. 4161/rna.36281)
82. Luo GZ et al. 2014 Unique features of the m6A methylome in Arabidopsis thaliana. Nat. Commun. 5, 5630. (doi:10.1038/ncomms6630)
83. 6-methyladenosine methylation in post-transcriptional gene expression regulation. Genes Dev. 29, 1343–1355. (doi:10. 1101/gad.262766.115)
84. 6A: a novel hallmark of translation. Cell Cycle 15, 309–310. (doi:10.1080/15384101.2015.1125240)
85. Hinnebusch AG. 2014 The scanning mechanism of eukaryotic translation initiation. Annu. Rev. Biochem. 83, 779–812. (doi:10.1146/annurev-biochem-060713-035802)
86. Martin KC, Zukin RS. 2006 RNA trafficking and local protein synthesis in dendrites: an overview. J. Neurosci. 26, 7131–7134. (doi:10.1523/ JNEUROSCI.1801-06.2006)
87. Ingolia NT. 2014 Ribosome profiling: new views of translation, from single codons to genome scale. Nat. Rev. Genet. 15, 205–213. (doi:10.1038/ nrg3645)
88. Hussain S, Bashir ZI. 2015 The epitranscriptome in modulating spatiotemporal RNA translation in neuronal post-synaptic function. Front. Cell Neurosci. 9, 420. (doi:10.3389/fncel.2015.00420)
89. Walters BJ, Mercaldo V, Gillon CJ, Yip M, Neve RL, Boyce FM, Frankland PW, Josselyn SA. 2017 The role of The RNA demethylase FTO (Fat Mass and Obesity-Associated) and mRNA methylation in hippocampal memory formation. Neuropsychopharmacology 42, 1502–1510. (doi:10. 1038/npp.2017.31)
90. Du T, Rao S, Wu L, Ye N, Liu Z, Hu H, Xiu J, Shen Y, Xu Q. 2015 An association study of the m6A genes with major depressive disorder in Chinese Han population. J. Affect. Disorders 183, 279–286. (doi:10.1016/j.jad.2015.05.025)
91. Keller L, Xu W, Wang HX, Winblad B, Fratiglioni L, Graff C. 2011 The obesity related gene, FTO, interacts with APOE, and is associated with Alzheimer’s Dis. risk: a prospective cohort study. J. Alzheimer’s Dis. 23, 461–469. (doi:10.3233/JAD-2010-101068)
92. Reitz C et al. 2012 Genetic variants in the Fat and Obesity Associated (FTO) gene and risk of Alzheimer’s disease. PLoS ONE 7, e50354. (doi:10. 1371/journal.pone.0050354)