Characterizing 5-methylcytosine in the mammalian epitranscriptome

The post-transcriptional modification 5-methylcytosine (m5C) occurs in a wide range of coding and non-coding RNAs. We describe transcriptome-wide approaches to capture the global m5C RNA methylome. We also discuss the potential functions of m5C in RNA and compare them to 6-methyladenosine modifications.

[1]  Schraga Schwartz,et al.  Transcriptome-Wide Mapping of 5-methylcytidine RNA Modifications in Bacteria, Archaea, and Yeast Reveals m5C within Archaeal mRNAs , 2013, PLoS genetics.

[2]  Nicholas T. Ingolia,et al.  Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity and Dynamics of Mammalian Proteomes , 2011, Cell.

[3]  P. Agris,et al.  5-Methylcytidine is required for cooperative binding of Mg2+ and a conformational transition at the anticodon stem-loop of yeast phenylalanine tRNA. , 1993, Biochemistry.

[4]  P. Barr,et al.  On the mechanism of inhibition of DNA-cytosine methyltransferases by cytosine analogs , 1983, Cell.

[5]  R. Desrosiers,et al.  Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. , 1974, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Roger D. Cox,et al.  Overexpression of Fto leads to increased food intake and results in obesity , 2010, Nature Genetics.

[7]  Yaoquan Liu,et al.  RNA and m 5 C DNA methyl transferases use different cysteine residues as catalysts , 2000 .

[8]  Izabela Makałowska,et al.  Identification of human tRNA:m5C methyltransferase catalysing intron-dependent m5C formation in the first position of the anticodon of the pre-tRNA(CAA)Leu , 2006, Nucleic acids research.

[9]  C. Taylor,et al.  Nucleolar protein p120 contains an arginine-rich domain that binds to ribosomal RNA. , 1998, The Biochemical journal.

[10]  D T Dubin,et al.  The methylation state of poly A-containing messenger RNA from cultured hamster cells. , 1975, Nucleic acids research.

[11]  H. Ropers,et al.  Autosomal recessive mental retardation: homozygosity mapping identifies 27 single linkage intervals, at least 14 novel loci and several mutation hotspots , 2011, Human Genetics.

[12]  Alexander Meissner,et al.  Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. , 2010, Cell stem cell.

[13]  B. Maden.  Locations of methyl groups in 28 S rRNA of Xenopus laevis and man. Clustering in the conserved core of molecule. , 1988, Journal of molecular biology.

[14]  S. K. Mahto,et al.  Expanding the nucleotide repertoire of the ribosome with post-transcriptional modifications. , 2007, ACS chemical biology.

[15]  T. Preiss,et al.  Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA , 2012, Nucleic acids research.

[16]  F. Watt,et al.  The RNA Methyltransferase Misu (NSun2) Mediates Myc-Induced Proliferation and Is Upregulated in Tumors , 2006, Current Biology.

[17]  K. Redman.  Assembly of protein-RNA complexes using natural RNA and mutant forms of an RNA cytosine methyltransferase. , 2006, Biomacromolecules.

[18]  Weifeng Gu,et al.  Rapid tRNA decay can result from lack of nonessential modifications. , 2006, Molecular cell.

[19]  D. Lowenstein,et al.  Epilepsy genetics--past, present, and future. , 2011, Current opinion in genetics & development.

[20]  Michaela Frye,et al.  Genomic gain of 5p15 leads to over-expression of Misu (NSUN2) in breast cancer. , 2010, Cancer letters.

[21]  Dagmar Wieczorek,et al.  Mutations in NSUN2 cause autosomal-recessive intellectual disability. , 2012, American journal of human genetics.

[22]  M. Gorospe,et al.  The tRNA methyltransferase NSun2 stabilizes p16INK4 mRNA by methylating the 3′-untranslated region of p16 , 2012, Nature Communications.

[23]  Michaela Frye,et al.  The Mouse Cytosine-5 RNA Methyltransferase NSun2 Is a Component of the Chromatoid Body and Required for Testis Differentiation , 2013, Molecular and Cellular Biology.

[24]  Bianca Habermann,et al.  Structure of the human MTERF4–NSUN4 protein complex that regulates mitochondrial ribosome biogenesis , 2012, Proceedings of the National Academy of Sciences.

[25]  Frank Lyko,et al.  5-methylcytosine in RNA: detection, enzymatic formation and biological functions , 2009, Nucleic acids research.

[26]  B. Habermann,et al.  MTERF4 regulates translation by targeting the methyltransferase NSUN4 to the mammalian mitochondrial ribosome. , 2011, Cell metabolism.

[27]  B. Hong,et al.  Nop2p is required for pre-rRNA processing and 60S ribosome subunit synthesis in yeast , 1997, Molecular and cellular biology.

[28]  B. Moss,et al.  Methylated nucleotides block 5′ terminus of HeLa cell messenger RNA , 1975, Cell.

[29]  K. Redman,et al.  RNA methyltransferases utilize two cysteine residues in the formation of 5-methylcytosine. , 2002, Biochemistry.

[30]  J E Darnell,et al.  Methylated, blocked 5 termini in HeLa cell mRNA. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[31]  D. Santi,et al.  Exposition of a family of RNA m(5)C methyltransferases from searching genomic and proteomic sequences. , 1999, Nucleic acids research.

[32]  Isabelle Behm-Ansmant,et al.  Use of Specific Chemical Reagents for Detection of Modified Nucleotides in RNA , 2011, Journal of nucleic acids.

[33]  Z. Nawaz,et al.  Whole exome sequencing unravels disease‐causing genes in consanguineous families in Qatar , 2014, Clinical genetics.

[34]  A. Doll,et al.  Characterization of two novel genes, WBSCR20 and WBSCR22, deleted in Williams-Beuren syndrome , 2002, Cytogenetic and Genome Research.

[35]  D. Licatalosi,et al.  FMRP Stalls Ribosomal Translocation on mRNAs Linked to Synaptic Function and Autism , 2011, Cell.

[36]  S. Gabriel,et al.  Whole exome sequencing identifies a splicing mutation in NSUN2 as a cause of a Dubowitz-like syndrome , 2012, Journal of Medical Genetics.

[37]  Suzanne Cory,et al.  Modified nucleosides and bizarre 5′-termini in mouse myeloma mRNA , 1975, Nature.

[38]  O. Elemento,et al.  Comprehensive Analysis of mRNA Methylation Reveals Enrichment in 3′ UTRs and near Stop Codons , 2012, Cell.

[39]  M. Helm,et al.  tRNA stabilization by modified nucleotides. , 2010, Biochemistry.

[40]  W. Zhang,et al.  Increased growth of NIH/3T3 cells by transfection with human p120 complementary DNA and inhibition by a p120 antisense construct. , 1992, Cancer research.

[41]  F. Rottman,et al.  Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. , 1997, RNA.

[42]  Frank Lyko,et al.  RNA cytosine methylation analysis by bisulfite sequencing , 2008, Nucleic acids research.

[43]  P. Delgado-Olguín,et al.  Expression of NOL1/NOP2/sun domain (Nsun) RNA methyltransferase family genes in early mouse embryogenesis. , 2013, Gene expression patterns : GEP.

[44]  J. Nichols,et al.  The RNA–Methyltransferase Misu (NSun2) Poises Epidermal Stem Cells to Differentiate , 2011, PLoS genetics.

[45]  J. Bujnicki,et al.  MODOMICS: a database of RNA modification pathways—2013 update , 2012, Nucleic Acids Res..

[46]  J. Ule,et al.  iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution , 2010, Nature Structural &Molecular Biology.

[47]  Bradley R. Cairns,et al.  Identification of direct targets and modified bases of RNA cytosine methyltransferases , 2013, Nature Biotechnology.

[48]  D. Santi,et al.  m5C RNA and m5C DNA methyl transferases use different cysteine residues as catalysts. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[49]  J. Hurwitz,et al.  Messenger RNA. , 1962, Scientific American.

[50]  Donald Grierson,et al.  Yeast targets for mRNA methylation , 2010, Nucleic acids research.

[51]  J. Schimenti,et al.  Sperm Motility Defects and Infertility in Male Mice with a Mutation in Nsun7, a Member of the Sun Domain-Containing Family of Putative RNA Methyltransferases1 , 2007, Biology of reproduction.

[52]  M. Tatsuka,et al.  Aurora-B regulates RNA methyltransferase NSUN2. , 2007, Molecular biology of the cell.

[53]  A. Bird,et al.  DNA methylation landscapes: provocative insights from epigenomics , 2008, Nature Reviews Genetics.

[54]  J. Freeman,et al.  Intranucleolar localization of human proliferating cell nucleolar antigen p120. , 1988, Cancer research.

[55]  Simon Hess,et al.  The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry , 2013, Nature Neuroscience.

[56]  Patricia P. Chan,et al.  GtRNAdb: a database of transfer RNA genes detected in genomic sequence , 2008, Nucleic Acids Res..

[57]  Clement T Y Chan,et al.  Reprogramming of tRNA modifications controls the oxidative stress response by codon-biased translation of proteins , 2012, Nature Communications.

[58]  B. Hong,et al.  Yeast NOP2 encodes an essential nucleolar protein with homology to a human proliferation marker , 1994, Journal of Cell Biology.

[59]  Marcin Feder,et al.  MODOMICS: a database of RNA modification pathways , 2005, Nucleic Acids Res..

[60]  R. Planta,et al.  The primary and secondary structure of yeast 26S rRNA. , 1981, Nucleic acids research.

[61]  Chengqi Yi,et al.  Analysis of RNA base modification and structural rearrangement by single-molecule real-time detection of reverse transcription , 2013, Journal of Nanobiotechnology.

[62]  D. Santi,et al.  Kinetic and catalytic mechanism of HhaI methyltransferase. , 1987, The Journal of biological chemistry.

[63]  E. Phizicky,et al.  Degradation of several hypomodified mature tRNA species in Saccharomyces cerevisiae is mediated by Met22 and the 5'-3' exonucleases Rat1 and Xrn1. , 2008, Genes & development.

[64]  Jernej Ule,et al.  NSun2-Mediated Cytosine-5 Methylation of Vault Noncoding RNA Determines Its Processing into Regulatory Small RNAs , 2013, Cell reports.

[65]  Kathleen R. Noon,et al.  Posttranscriptional Modifications in 16 S and 23 S rRNAs of the Archaeal Hyperthermophile Sulfolobus solfataricus , 1998 .

[66]  A. Shatkin,et al.  Methylated simian virus 40-specific RNA from nuclei and cytoplasm of infected BSC-1 cells. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[67]  A. Noor,et al.  Mutation in NSUN2, which encodes an RNA methyltransferase, causes autosomal-recessive intellectual disability. , 2012, American journal of human genetics.

[68]  F. Tuorto,et al.  RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis , 2012, Nature Structural &Molecular Biology.

[69]  David C Reutens,et al.  Research Review: Williams syndrome: a critical review of the cognitive, behavioral, and neuroanatomical phenotype. , 2008, Journal of child psychology and psychiatry, and allied disciplines.

[70]  Francesca Tuorto,et al.  RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage. , 2010, Genes & development.

[71]  V. Stollar,et al.  Sindbis virus messenger RNA: the 5'-termini and methylated residues of 26 and 42 S RNA. , 1977, Virology.

[72]  S. Eddy,et al.  tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence. , 1997, Nucleic acids research.

[73]  Norman E. Davey,et al.  Insights into RNA Biology from an Atlas of Mammalian mRNA-Binding Proteins , 2012, Cell.

[74]  Minoru Yoshida,et al.  RNA-Methylation-Dependent RNA Processing Controls the Speed of the Circadian Clock , 2013, Cell.

[75]  L. E. McDonald,et al.  A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[76]  B. Cairns,et al.  Dnmt2 functions in the cytoplasm to promote liver, brain, and retina development in zebrafish. , 2007, Genes & development.

[77]  Mauricio O. Carneiro,et al.  The advantages of SMRT sequencing , 2013, Genome Biology.

[78]  W. Jelinek,et al.  Methyl labeling of HeLa cell hnRNA: a comparison with mRNA , 1976, Cell.

[79]  I. Dragoni,et al.  The nucleolar RNA methyltransferase Misu (NSun2) is required for mitotic spindle stability , 2009, The Journal of cell biology.

[80]  M. Kupiec,et al.  Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq , 2012, Nature.

[81]  P. Mitchell,et al.  Methylation sites in Escherichia coli ribosomal RNA: localization and identification of four new sites of methylation in 23S rRNA. , 1992, Biochemistry.

[82]  J. Freeman,et al.  Identification and characterization of a human proliferation-associated nucleolar antigen with a molecular weight of 120,000 expressed in early G1 phase. , 1988, Cancer research.