Home LiteratureArticle Details
PMID: 31110512 Published · epublish English Journal Article Review

Epitranscriptomic RNA Methylation in Plant Development and Abiotic Stress Responses.

Frontiers in plant science ·Vol. 10 ·2019-00-00 ·Pages 500

Hu J, Manduzio S, Kang H

Abstract

Recent advances in methylated RNA immunoprecipitation followed by sequencing and mass spectrometry have revealed widespread chemical modifications on mRNAs. Methylation of RNA bases such as N 6-methyladenosine (m6A) and 5-methylcytidine (m5C) is the most prevalent mRNA modifications found in eukaryotes. In recent years, cellular factors introducing, interpreting, and deleting specific methylation marks on mRNAs, designated as "writers (methyltransferase)," "readers (RNA-binding protein)," and "erasers (demethylase)," respectively, have been identified in plants and animals. An emerging body of evidence shows that methylation on mRNAs affects diverse aspects of RNA metabolism, including stability, splicing, nucleus-to-cytoplasm export, alternative polyadenylation, and translation. Although our understanding for roles of writers, readers, and erasers in plants is far behind that for their animal counterparts, accumulating reports clearly demonstrate that these factors are essential for plant growth and abiotic stress responses. This review emphasizes the crucial roles of epitranscriptomic modifications of RNAs in new layer of gene expression regulation during the growth and response of plants to abiotic stresses.

Keywords
RNA metabolism RNA methylation RNA modification abiotic stress epitranscriptome
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hu Jianzhong
Department of Applied Biology, College of Agriculture and Life Sciences, Chonnam National University, Gwangju, South Korea.
Manduzio Stefano
Department of Applied Biology, College of Agriculture and Life Sciences, Chonnam National University, Gwangju, South Korea.
Kang Hunseung
Department of Applied Biology, College of Agriculture and Life Sciences, Chonnam National University, Gwangju, South Korea.
References (104)
104 references, click to expand
  1. Molecular identification of virilizer, a gene required for the expression of the sex-determining gene Sex-lethal in Drosophila melanogaster.
    Genetics. 2001 Feb;157(2):679-88 PMID: 11156988
  2. IME4, a gene that mediates MAT and nutritional control of meiosis in Saccharomyces cerevisiae.
    Mol Cell Biol. 1992 Mar;12(3):1078-86 PMID: 1545790
  3. Dissecting salt stress pathways.
    J Exp Bot. 2006;57(5):1097-107 PMID: 16510518
  4. The RNA methyltransferase Misu (NSun2) mediates Myc-induced proliferation and is upregulated in tumors.
    Curr Biol. 2006 May 23;16(10):971-81 PMID: 16713953
  5. MTA is an Arabidopsis messenger RNA adenosine methylase and interacts with a homolog of a sex-specific splicing factor.
    Plant Cell. 2008 May;20(5):1278-88 PMID: 18505803
  6. Human AlkB homolog 1 is a mitochondrial protein that demethylates 3-methylcytosine in DNA and RNA.
    J Biol Chem. 2008 Sep 5;283(36):25046-56 PMID: 18603530
  7. RNA cytosine methylation analysis by bisulfite sequencing.
    Nucleic Acids Res. 2009 Feb;37(2):e12 PMID: 19059995
  8. Karrikins enhance light responses during germination and seedling development in Arabidopsis thaliana.
    Proc Natl Acad Sci U S A. 2010 Apr 13;107(15):7095-100 PMID: 20351290
  9. The RNA Modification Database, RNAMDB: 2011 update.
    Nucleic Acids Res. 2011 Jan;39(Database issue):D195-201 PMID: 21071406
  10. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO.
    Nat Chem Biol. 2011 Oct 16;7(12):885-7 PMID: 22002720
  11. Crystal structure and RNA binding properties of the RNA recognition motif (RRM) and AlkB domains in human AlkB homolog 8 (ABH8), an enzyme catalyzing tRNA hypermodification.
    J Biol Chem. 2012 Jan 13;287(3):2130-43 PMID: 22065580
  12. Novel AlkB dioxygenases--alternative models for in silico and in vivo studies.
    PLoS One. 2012;7(1):e30588 PMID: 22291995
  13. Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA.
    Nucleic Acids Res. 2012 Jun;40(11):5023-33 PMID: 22344696
  14. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq.
    Nature. 2012 Apr 29;485(7397):201-6 PMID: 22575960
  15. Adenosine Methylation in Arabidopsis mRNA is Associated with the 3' End and Reduced Levels Cause Developmental Defects.
    Front Plant Sci. 2012 Mar 23;3:48 PMID: 22639649
  16. ALKBH1 is a histone H2A dioxygenase involved in neural differentiation.
    Stem Cells. 2012 Dec;30(12):2672-82 PMID: 22961808
  17. The birth of the Epitranscriptome: deciphering the function of RNA modifications.
    Genome Biol. 2012 Oct 31;13(10):175 PMID: 23113984
  18. Transfer RNA modifications: nature's combinatorial chemistry playground.
    Wiley Interdiscip Rev RNA. 2013 Jan-Feb;4(1):35-48 PMID: 23139145
  19. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility.
    Mol Cell. 2013 Jan 10;49(1):18-29 PMID: 23177736
  20. The mouse cytosine-5 RNA methyltransferase NSun2 is a component of the chromatoid body and required for testis differentiation.
    Mol Cell Biol. 2013 Apr;33(8):1561-70 PMID: 23401851
  21. m(6)A mRNA methylation: a new circadian pacesetter.
    Cell. 2013 Nov 7;155(4):740-1 PMID: 24209613
  22. RNA-methylation-dependent RNA processing controls the speed of the circadian clock.
    Cell. 2013 Nov 7;155(4):793-806 PMID: 24209618
  23. N6-methyladenosine-dependent regulation of messenger RNA stability.
    Nature. 2014 Jan 2;505(7481):117-20 PMID: 24284625
  24. Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase.
    Cell Res. 2014 Feb;24(2):177-89 PMID: 24407421
  25. The dynamic epitranscriptome: N6-methyladenosine and gene expression control.
    Nat Rev Mol Cell Biol. 2014 May;15(5):313-26 PMID: 24713629
  26. Perturbation of m6A writers reveals two distinct classes of mRNA methylation at internal and 5' sites.
    Cell Rep. 2014 Jul 10;8(1):284-96 PMID: 24981863
  27. Molecular basis for the recognition of methylated adenines in RNA by the eukaryotic YTH domain.
    Proc Natl Acad Sci U S A. 2014 Sep 23;111(38):13834-9 PMID: 25201973
  28. Structural basis for selective binding of m6A RNA by the YTHDC1 YTH domain.
    Nat Chem Biol. 2014 Nov;10(11):927-9 PMID: 25242552
  29. Decreased N(6)-methyladenosine in peripheral blood RNA from diabetic patients is associated with FTO expression rather than ALKBH5.
    J Clin Endocrinol Metab. 2015 Jan;100(1):E148-54 PMID: 25303482
  30. FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis.
    Cell Res. 2014 Dec;24(12):1403-19 PMID: 25412662
  31. Unique features of the m6A methylome in Arabidopsis thaliana.
    Nat Commun. 2014 Nov 28;5:5630 PMID: 25430002
  32. Transcriptome-wide N⁶-methyladenosine profiling of rice callus and leaf reveals the presence of tissue-specific competitors involved in selective mRNA modification.
    RNA Biol. 2014;11(9):1180-8 PMID: 25483034
  33. Stem cells. m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation.
    Science. 2015 Feb 27;347(6225):1002-6 PMID: 25569111
  34. KH-RNA interactions: back in the groove.
    Curr Opin Struct Biol. 2015 Feb;30:63-70 PMID: 25625331
  35. m(6)A RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency.
    Cell Stem Cell. 2015 Mar 5;16(3):289-301 PMID: 25683224
  36. Heat-induced ribosome pausing triggers mRNA co-translational decay in Arabidopsis thaliana.
    Nucleic Acids Res. 2015 Apr 30;43(8):4121-32 PMID: 25845591
  37. Non-homologous functions of the AlkB homologs.
    J Mol Cell Biol. 2015 Dec;7(6):494-504 PMID: 26003568
  38. N(6)-methyladenosine Modulates Messenger RNA Translation Efficiency.
    Cell. 2015 Jun 4;161(6):1388-99 PMID: 26046440
  39. The AlkB Family of Fe(II)/α-Ketoglutarate-dependent Dioxygenases: Repairing Nucleic Acid Alkylation Damage and Beyond.
    J Biol Chem. 2015 Aug 21;290(34):20734-42 PMID: 26152727
  40. RNA N6-methyladenosine methylation in post-transcriptional gene expression regulation.
    Genes Dev. 2015 Jul 1;29(13):1343-55 PMID: 26159994
  41. HNRNPA2B1 Is a Mediator of m(6)A-Dependent Nuclear RNA Processing Events.
    Cell. 2015 Sep 10;162(6):1299-308 PMID: 26321680
  42. 'View From A Bridge': A New Perspective on Eukaryotic rRNA Base Modification.
    Trends Biochem Sci. 2015 Oct;40(10):560-575 PMID: 26410597
  43. Dynamic m(6)A mRNA methylation directs translational control of heat shock response.
    Nature. 2015 Oct 22;526(7574):591-4 PMID: 26458103
  44. 5' UTR m(6)A Promotes Cap-Independent Translation.
    Cell. 2015 Nov 5;163(4):999-1010 PMID: 26593424
  45. Loss of FTO in adipose tissue decreases Angptl4 translation and alters triglyceride metabolism.
    Sci Signal. 2015 Dec 15;8(407):ra127 PMID: 26671148
  46. N(6)-methyladenosine in mRNA disrupts tRNA selection and translation-elongation dynamics.
    Nat Struct Mol Biol. 2016 Feb;23(2):110-5 PMID: 26751643
  47. N6-methyladenosine–encoded epitranscriptomics.
    Nat Struct Mol Biol. 2016 Feb;23(2):98-102 PMID: 26840897
  48. The dynamic N(1)-methyladenosine methylome in eukaryotic messenger RNA.
    Nature. 2016 Feb 25;530(7591):441-6 PMID: 26863196
  49. Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing.
    Mol Cell. 2016 Feb 18;61(4):507-519 PMID: 26876937
  50. Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m⁶A-demethylation of NANOG mRNA.
    Proc Natl Acad Sci U S A. 2016 Apr 5;113(14):E2047-56 PMID: 27001847
  51. DNA methylation on N(6)-adenine in mammalian embryonic stem cells.
    Nature. 2016 Apr 21;532(7599):329-33 PMID: 27027282
  52. The m(6)A Methyltransferase METTL3 Promotes Translation in Human Cancer Cells.
    Mol Cell. 2016 May 5;62(3):335-345 PMID: 27117702
  53. ALKBHs-facilitated RNA modifications and de-modifications.
    DNA Repair (Amst). 2016 Aug;44:87-91 PMID: 27237585
  54. Structural basis of N(6)-adenosine methylation by the METTL3-METTL14 complex.
    Nature. 2016 May 25;534(7608):575-8 PMID: 27281194
  55. Messenger RNA modifications: Form, distribution, and function.
    Science. 2016 Jun 17;352(6292):1408-12 PMID: 27313037
  56. N(6)-Methyladenosine RNA Modification Regulates Shoot Stem Cell Fate in Arabidopsis.
    Dev Cell. 2016 Jul 25;38(2):186-200 PMID: 27396363
  57. YTHDF2 destabilizes m(6)A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex.
    Nat Commun. 2016 Aug 25;7:12626 PMID: 27558897
  58. Structural insights into the molecular mechanism of the m(6)A writer complex.
    Elife. 2016 Sep 14;5: PMID: 27627798
  59. Tuning the ribosome: The influence of rRNA modification on eukaryotic ribosome biogenesis and function.
    RNA Biol. 2017 Sep 2;14(9):1138-1152 PMID: 27911188
  60. m6A modulates neuronal functions and sex determination in Drosophila.
    Nature. 2016 Dec 8;540(7632):242-247 PMID: 27919077
  61. m6A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination.
    Nature. 2016 Dec 8;540(7632):301-304 PMID: 27919081
  62. Reversible methylation of m6Am in the 5' cap controls mRNA stability.
    Nature. 2017 Jan 19;541(7637):371-375 PMID: 28002401
  63. FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a N6-Methyladenosine RNA Demethylase.
    Cancer Cell. 2017 Jan 9;31(1):127-141 PMID: 28017614
  64. Cytosine-5 RNA Methylation Regulates Neural Stem Cell Differentiation and Motility.
    Stem Cell Reports. 2017 Jan 10;8(1):112-124 PMID: 28041877
  65. Transcriptome-Wide Mapping of RNA 5-Methylcytosine in Arabidopsis mRNAs and Noncoding RNAs.
    Plant Cell. 2017 Mar;29(3):445-460 PMID: 28062751
  66. YTHDF3 facilitates translation and decay of N6-methyladenosine-modified RNA.
    Cell Res. 2017 Mar;27(3):315-328 PMID: 28106072
  67. AlkB homolog 3-mediated tRNA demethylation promotes protein synthesis in cancer cells.
    Sci Rep. 2017 Feb 13;7:42271 PMID: 28205560
  68. m1A Post-Transcriptional Modification in tRNAs.
    Biomolecules. 2017 Feb 21;7(1): PMID: 28230814
  69. RNA m6A methylation regulates the ultraviolet-induced DNA damage response.
    Nature. 2017 Mar 23;543(7646):573-576 PMID: 28297716
  70. Chemical and Conformational Diversity of Modified Nucleosides Affects tRNA Structure and Function.
    Biomolecules. 2017 Mar 16;7(1): PMID: 28300792
  71. FTO is required for myogenesis by positively regulating mTOR-PGC-1α pathway-mediated mitochondria biogenesis.
    Cell Death Dis. 2017 Mar 23;8(3):e2702 PMID: 28333151
  72. m6A Demethylase ALKBH5 Maintains Tumorigenicity of Glioblastoma Stem-like Cells by Sustaining FOXM1 Expression and Cell Proliferation Program.
    Cancer Cell. 2017 Apr 10;31(4):591-606.e6 PMID: 28344040
  73. ALKBH1 is an RNA dioxygenase responsible for cytoplasmic and mitochondrial tRNA modifications.
    Nucleic Acids Res. 2017 Jul 7;45(12):7401-7415 PMID: 28472312
  74. Identification of factors required for m6 A mRNA methylation in Arabidopsis reveals a role for the conserved E3 ubiquitin ligase HAKAI.
    New Phytol. 2017 Jul;215(1):157-172 PMID: 28503769
  75. Readers, writers and erasers of N6-methylated adenosine modification.
    Curr Opin Struct Biol. 2017 Dec;47:67-76 PMID: 28624569
  76. Rethinking m6A Readers, Writers, and Erasers.
    Annu Rev Cell Dev Biol. 2017 Oct 6;33:319-342 PMID: 28759256
  77. Ythdc2 is an N6-methyladenosine binding protein that regulates mammalian spermatogenesis.
    Cell Res. 2017 Sep;27(9):1115-1127 PMID: 28809393
  78. N6-methyladenosine (m6A) recruits and repels proteins to regulate mRNA homeostasis.
    Nat Struct Mol Biol. 2017 Oct;24(10):870-878 PMID: 28869609
  79. Arabidopsis m6A demethylase activity modulates viral infection of a plant virus and the m6A abundance in its genomic RNAs.
    Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):10755-10760 PMID: 28923956
  80. 5-Methylcytosine RNA Methylation in Arabidopsis Thaliana.
    Mol Plant. 2017 Nov 6;10(11):1387-1399 PMID: 28965832
  81. N6-methyladenosine demethylase FTO targets pre-mRNAs and regulates alternative splicing and 3'-end processing.
    Nucleic Acids Res. 2017 Nov 2;45(19):11356-11370 PMID: 28977517
  82. The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution.
    Nature. 2017 Nov 9;551(7679):251-255 PMID: 29072297
  83. Characterization of human AlkB homolog 1 produced in mammalian cells and demonstration of mitochondrial dysfunction in ALKBH1-deficient cells.
    Biochem Biophys Res Commun. 2018 Jan 1;495(1):98-103 PMID: 29097205
  84. MODOMICS: a database of RNA modification pathways. 2017 update.
    Nucleic Acids Res. 2018 Jan 4;46(D1):D303-D307 PMID: 29106616
  85. RNA Chemical Proteomics Reveals the N6-Methyladenosine (m6A)-Regulated Protein-RNA Interactome.
    J Am Chem Soc. 2017 Dec 6;139(48):17249-17252 PMID: 29140688
  86. ALKBH10B Is an RNA N6-Methyladenosine Demethylase Affecting Arabidopsis Floral Transition.
    Plant Cell. 2017 Dec;29(12):2995-3011 PMID: 29180595
  87. Transcriptome-wide Analysis of Roles for tRNA Modifications in Translational Regulation.
    Mol Cell. 2017 Dec 7;68(5):978-992.e4 PMID: 29198561
  88. ALKBH5-dependent m6A demethylation controls splicing and stability of long 3'-UTR mRNAs in male germ cells.
    Proc Natl Acad Sci U S A. 2018 Jan 9;115(2):E325-E333 PMID: 29279410
  89. ketu mutant mice uncover an essential meiotic function for the ancient RNA helicase YTHDC2.
    Elife. 2018 Jan 23;7: PMID: 29360036
  90. N6-methyladenosine links RNA metabolism to cancer progression.
    Cell Death Dis. 2018 Jan 26;9(2):124 PMID: 29374143
  91. Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation.
    Nat Cell Biol. 2018 Mar;20(3):285-295 PMID: 29476152
  92. VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation.
    Cell Discov. 2018 Feb 27;4:10 PMID: 29507755
  93. Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-binding factor Rbm15/Spenito to the m6A machinery component Wtap/Fl(2)d.
    Genes Dev. 2018 Mar 1;32(5-6):415-429 PMID: 29535189
  94. Xio is a component of the Drosophila sex determination pathway and RNA N6-methyladenosine methyltransferase complex.
    Proc Natl Acad Sci U S A. 2018 Apr 3;115(14):3674-3679 PMID: 29555755
  95. Multiple functions of m6A RNA methylation in cancer.
    J Hematol Oncol. 2018 Mar 27;11(1):48 PMID: 29587823
  96. The YTH Domain Protein ECT2 Is an m6A Reader Required for Normal Trichome Branching in Arabidopsis.
    Plant Cell. 2018 May;30(5):986-1005 PMID: 29618631
  97. An m6A-YTH Module Controls Developmental Timing and Morphogenesis in Arabidopsis.
    Plant Cell. 2018 May;30(5):952-967 PMID: 29643069
  98. YTH Domain: A Family of N6-methyladenosine (m6A) Readers.
    Genomics Proteomics Bioinformatics. 2018 Apr;16(2):99-107 PMID: 29715522
  99. The m6A Reader ECT2 Controls Trichome Morphology by Affecting mRNA Stability in Arabidopsis.
    Plant Cell. 2018 May;30(5):968-985 PMID: 29716990
  100. Transcriptome-Wide Annotation of m5C RNA Modifications Using Machine Learning.
    Front Plant Sci. 2018 Apr 18;9:519 PMID: 29720995
  101. FTO, m6 Am , and the hypothesis of reversible epitranscriptomic mRNA modifications.
    FEBS Lett. 2018 Jun;592(12):2012-2022 PMID: 29754392
  102. Two Ck1δ transcripts regulated by m6A methylation code for two antagonistic kinases in the control of the circadian clock.
    Proc Natl Acad Sci U S A. 2018 Jun 5;115(23):5980-5985 PMID: 29784786
  103. The m6A-epitranscriptomic signature in neurobiology: from neurodevelopment to brain plasticity.
    J Neurochem. 2018 Oct;147(2):137-152 PMID: 29873074
  104. RNA methylation in nuclear pre-mRNA processing.
    Wiley Interdiscip Rev RNA. 2018 Nov;9(6):e1489 PMID: 29921017
Article Info
Journal
Frontiers in plant science
Abbr.
Front Plant Sci
ISSN
1664-462X
Published
2019-00-00
Epub
2019-00-17
Pages
500
Language
English
Region
Switzerland
NLM ID
101568200
PMCID
PMC6499213
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com