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tRNA methylation

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https://www.readbyqxmd.com/read/28335556/trm5-and-trmd-two-enzymes-from-distinct-origins-catalyze-the-identical-trna-modification-m%C3%A2-g37
#1
REVIEW
Sakurako Goto-Ito, Takuhiro Ito, Shigeyuki Yokoyama
The N¹-atom of guanosine at position 37 in transfer RNA (tRNA) is methylated by tRNA methyltransferase 5 (Trm5) in eukaryotes and archaea, and by tRNA methyltransferase D (TrmD) in bacteria. The resultant modified nucleotide m¹G37 positively regulates the aminoacylation of the tRNA, and simultaneously functions to prevent the +1 frameshift on the ribosome. Interestingly, Trm5 and TrmD have completely distinct origins, and therefore bear different tertiary folds. In this review, we describe the different strategies utilized by Trm5 and TrmD to recognize their substrate tRNAs, mainly based on their crystal structures complexed with substrate tRNAs...
March 21, 2017: Biomolecules
https://www.readbyqxmd.com/read/28290676/biochemical-characterization-of-ap-lyase-and-m-6-a-demethylase-activities-of-human-alkb-homolog-1-alkbh1
#2
Tina A Müller, Michael A Tobar, Madison N Perian, Robert P Hausinger
Alkbh1 is one of nine mammalian homologs of Escherichia coli AlkB, a 2-oxoglutarate-dependent dioxygenase that catalyzes direct DNA repair by removing alkyl lesions from DNA. Six distinct enzymatic activities have been reported for Alkbh1, including hydroxylation of variously methylated DNA, mRNA, tRNA, or histone substrates along with the cleavage of DNA at apurinic/apyrimidinic (AP) sites followed by covalent attachment to the 5'-product. The studies described here extend the biochemical characterization for two of these enzymatic activities using human ALKBH1: the AP lyase and 6-methyl adenine DNA demethylase activities...
March 14, 2017: Biochemistry
https://www.readbyqxmd.com/read/28281930/combined-trna-modification-defects-impair-protein-homeostasis-and-synthesis-of-the-yeast-prion-protein-rnq1
#3
Raffael Schaffrath, Roland Klassen
Modified nucleosides in tRNA anticodon loops such as 5-methoxy-carbonyl-methyl-2-thiouridine (mcm(5)s(2)U) and pseuduridine (Ψ) are thought to be required for an efficient decoding process. In Saccharomyces cerevisiae, the simultaneous presence of mcm(5)s(2)U and Ψ38 in tRNA(Gln)UUG was shown to mediate efficient synthesis of the Q/N rich [PIN(+)] prion forming protein Rnq1. (1) In the absence of these two tRNA modifications, higher than normal levels of hypomodified tRNA(Gln)UUG, but not its isoacceptor tRNA(Gln)CUG can restore Rnq1 synthesis...
January 2, 2017: Prion
https://www.readbyqxmd.com/read/28277934/the-modified-base-isopentenyladenosine-and-its-derivatives-in-trna
#4
Ulrich Schweizer, Simon Bohleber, Noelia Fradejas-Villar
Base 37 in tRNA, 3'-adjacent to the anticodon, is occupied by a purine base that is thought to stabilize codon recognition by stacking interactions on the first Watson-Crick base pair. If the first codon position forms an A.U or U·A base pair, the purine is likely further modified in all domains of life. One of the first base modifications found in tRNA is N(6)-isopentenyl adenosine (i(6)A) present in a fraction of tRNAs in bacteria and eukaryotes, which can be further modified to 2-methyl-thio-N(6)-isopentenyladenosine (ms(2)i(6)A) in a subset of tRNAs...
February 17, 2017: RNA Biology
https://www.readbyqxmd.com/read/28274239/occupational-exposure-to-particles-and-mitochondrial-dna-relevance-for-blood-pressure
#5
Yiyi Xu, Huiqi Li, Maria Hedmer, Mohammad Bakhtiar Hossain, Håkan Tinnerberg, Karin Broberg, Maria Albin
BACKGROUND: Particle exposure is a risk factor for cardiovascular diseases. Mitochondrial DNA (mtDNA) is a primary target for oxidative stress generated by particle exposure. We aimed to elucidate the effects of occupational exposure to particle-containing welding fumes on different biomarkers of mtDNA function, and in turn, explore if they modify the association between particle exposure and cardiovascular response, measured as blood pressure. METHODS: We investigated 101 welders and 127 controls (all non-smoking males) from southern Sweden...
March 9, 2017: Environmental Health: a Global Access Science Source
https://www.readbyqxmd.com/read/28264529/transfer%C3%A2-rna%C3%A2-methyltransferases%C3%A2-with%C3%A2-a%C3%A2-spou-trmd%C3%A2-spout-%C3%A2-fold%C3%A2-and%C3%A2-their%C3%A2-modified%C3%A2-nucleosides%C3%A2-in%C3%A2-trna
#6
REVIEW
Hiroyuki Hori
The existence of SpoU-TrmD (SPOUT) RNA methyltransferase superfamily was first predicted by bioinformatics. SpoU is the previous name of TrmH, which catalyzes the 2'-Omethylation of ribose of G18 in tRNA; TrmD catalyzes the formation of N1-methylguanosine at position 37 in tRNA. Although SpoU (TrmH) and TrmD were originally considered to be unrelated, the bioinformatics study suggested that they might share a common evolution origin and form a single superfamily. The common feature of SPOUT RNA methyltransferases is the formation of a deep trefoil knot in the catalytic domain...
February 28, 2017: Biomolecules
https://www.readbyqxmd.com/read/28257121/dealing%C3%A2-with%C3%A2-an%C3%A2-unconventional%C3%A2-genetic%C3%A2-code%C3%A2-in%C3%A2-mitochondria-%C3%A2-the%C3%A2-biogenesis%C3%A2-and%C3%A2-pathogenic%C3%A2-defects%C3%A2-of%C3%A2-the%C3%A2-5-formylcytosine%C3%A2-modification%C3%A2-in%C3%A2-mitochondrial%C3%A2-trna-met
#7
REVIEW
Lindsey Van Haute, Christopher A Powell, Michal Minczuk
Human mitochondria contain their own genome, which uses an unconventional genetic code. In addition to the standard AUG methionine codon, the single mitochondrial tRNA Methionine (mt-tRNAMet) also recognises AUA during translation initiation and elongation. Post-transcriptional modifications of tRNAs are important for structure, stability, correct folding and aminoacylation as well as decoding. The unique 5-formylcytosine (f5C) modification of position 34 in mt-tRNAMet has been long postulated to be crucial for decoding of unconventional methionine codons and efficient mitochondrial translation...
March 2, 2017: Biomolecules
https://www.readbyqxmd.com/read/28230814/m1a%C3%A2-post-transcriptional%C3%A2-modification%C3%A2-in%C3%A2-trnas
#8
REVIEW
Stephanie Oerum, Clément Dégut, Pierre Barraud, Carine Tisné
To date, about 90 post-transcriptional modifications have been reported in tRNA expanding their chemical and functional diversity. Methylation is the most frequent post-transcriptional tRNA modification that can occur on almost all nitrogen sites of the nucleobases, on the C5 atom of pyrimidines, on the C2 and C8 atoms of adenosine and, additionally, on the oxygen of the ribose 2'-OH. The methylation on the N1 atom of adenosine to form 1-methyladenosine (m1A) has been identified at nucleotide position 9, 14, 22, 57, and 58 in different tRNAs...
February 21, 2017: Biomolecules
https://www.readbyqxmd.com/read/28230119/editing-and-methylation-at-a-single-site-by-functionally-interdependent-activities
#9
Mary Anne T Rubio, Kirk W Gaston, Katherine M McKenney, Ian M C Fleming, Zdeněk Paris, Patrick A Limbach, Juan D Alfonzo
Nucleic acids undergo naturally occurring chemical modifications. Over 100 different modifications have been described and every position in the purine and pyrimidine bases can be modified; often the sugar is also modified. Despite recent progress, the mechanism for the biosynthesis of most modifications is not fully understood, owing, in part, to the difficulty associated with reconstituting enzyme activity in vitro. Whereas some modifications can be efficiently formed with purified components, others may require more intricate pathways...
February 22, 2017: Nature
https://www.readbyqxmd.com/read/28218716/sulfur-modifications-of-the-wobble-u34-in-trnas-and-their-intracellular-localization-in-eukaryotic-cells
#10
REVIEW
Yumi Nakai, Masato Nakai, Takato Yano
The wobble uridine (U34) of transfer RNAs (tRNAs) for two-box codon recognition, i.e., tRNA(Lys)UUU, tRNA(Glu)UUC, and tRNA(Gln)UUG, harbor a sulfur- (thio-) and a methyl-derivative structure at the second and fifth positions of U34, respectively. Both modifications are necessary to construct the proper anticodon loop structure and to enable them to exert their functions in translation. Thio-modification of U34 (s²U34) is found in both cytosolic tRNAs (cy-tRNAs) and mitochondrial tRNAs (mt-tRNAs). Although l-cysteine desulfurase is required in both cases, subsequent sulfur transfer pathways to cy-tRNAs and mt-tRNAs are different due to their distinct intracellular locations...
February 18, 2017: Biomolecules
https://www.readbyqxmd.com/read/28208788/next-generation%C3%A2-sequencing-based%C3%A2-ribomethseq%C3%A2-protocol%C3%A2-for%C3%A2-analysis%C3%A2-of%C3%A2-trna%C3%A2-2-o-methylation
#11
Virginie Marchand, Florian Pichot, Kathrin Thüring, Lilia Ayadi, Isabel Freund, Alexander Dalpke, Mark Helm, Yuri Motorin
Analysis of RNA modifications by traditional physico-chemical approaches is labor  intensive,  requires  substantial  amounts  of  input  material  and  only  allows  site-by-site  measurements.  The  recent  development  of  qualitative  and  quantitative  approaches  based  on   next-generation sequencing (NGS) opens new perspectives for the analysis of various cellular RNA  species.  The  Illumina  sequencing-based  RiboMethSeq  protocol  was  initially  developed  and  successfully applied for mapping of ribosomal RNA (rRNA) 2'-O-methylations...
February 9, 2017: Biomolecules
https://www.readbyqxmd.com/read/28208632/cross-talk-between-dnmt2-dependent-trna-methylation-and-queuosine-modification
#12
REVIEW
Ann E Ehrenhofer-Murray
Enzymes of the Dnmt2 family of methyltransferases have yielded a number of unexpected discoveries. The first surprise came more than ten years ago when it was realized that, rather than being DNA methyltransferases, Dnmt2 enzymes actually are transfer RNA (tRNA) methyltransferases for cytosine-5 methylation, foremost C38 (m5C38) of tRNAAsp. The second unanticipated finding was our recent discovery of a nutritional regulation of Dnmt2 in the fission yeast Schizosaccharomyces pombe. Significantly, the presence of the nucleotide queuosine in tRNAAsp strongly stimulates Dnmt2 activity both in vivo and in vitro in S...
February 10, 2017: Biomolecules
https://www.readbyqxmd.com/read/28205560/alkb-homolog-3-mediated-trna-demethylation-promotes-protein-synthesis-in-cancer-cells
#13
Yuko Ueda, Ikumi Ooshio, Yasuyuki Fusamae, Kaori Kitae, Megumi Kawaguchi, Kentaro Jingushi, Hiroaki Hase, Kazuo Harada, Kazumasa Hirata, Kazutake Tsujikawa
The mammalian AlkB homolog (ALKBH) family of proteins possess a 2-oxoglutarate- and Fe(II)-dependent oxygenase domain. A similar domain in the Escherichia coli AlkB protein catalyzes the oxidative demethylation of 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) in both DNA and RNA. AlkB homolog 3 (ALKBH3) was also shown to demethylate 1-meA and 3-meC (induced in single-stranded DNA and RNA by a methylating agent) to reverse the methylation damage and retain the integrity of the DNA/RNA. We previously reported the high expression of ALKBH3 in clinical tumor specimens and its involvement in tumor progression...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28134793/trm112-a-protein-activator-of-methyltransferases-modifying-actors-of-the-eukaryotic-translational-apparatus
#14
REVIEW
Gabrielle Bourgeois, Juliette Létoquart, Nhan van Tran, Marc Graille
Post-transcriptional and post-translational modifications are very important for the control and optimal efficiency of messenger RNA (mRNA) translation. Among these, methylation is the most widespread modification, as it is found in all domains of life. These methyl groups can be grafted either on nucleic acids (transfer RNA (tRNA), ribosomal RNA (rRNA), mRNA, etc.) or on protein translation factors. This review focuses on Trm112, a small protein interacting with and activating at least four different eukaryotic methyltransferase (MTase) enzymes modifying factors involved in translation...
January 27, 2017: Biomolecules
https://www.readbyqxmd.com/read/28119416/human-bcdin3d-monomethylates-cytoplasmic-histidine-transfer-rna
#15
Anna Martinez, Seisuke Yamashita, Takashi Nagaike, Yuriko Sakaguchi, Tsutomu Suzuki, Kozo Tomita
Human RNA methyltransferase BCDIN3D is overexpressed in breast cancer cells, and is related to the tumorigenic phenotype and poor prognosis of breast cancer. Here, we show that cytoplasmic tRNA(His) is the primary target of BCDIN3D in human cells. Recombinant human BCDIN3D, expressed in Escherichia coli, monomethylates the 5'-monophosphate of cytoplasmic tRNA(His) efficiently in vitro In BCDN3D-knockout cells, established by CRISPR/Cas9 editing, the methyl moiety at the 5'-monophosphate of cytoplasmic tRNA(His) is lost, and the exogenous expression of BCDIN3D in the knockout cells restores the modification in cytoplasmic tRNA(His) BCIDN3D recognizes the 5'-guanosine nucleoside at position -1 (G-1) and the eight-nucleotide acceptor helix with the G-1-A73 mis-pair at the top of the acceptor stem of cytoplasmic tRNA(His), which are exceptional structural features among cytoplasmic tRNA species...
January 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28108655/the-novel-lysine-specific-methyltransferase-mettl21b-affects-mrna-translation-through-inducible-and-dynamic-methylation-of-lys-165-in-human-eukaryotic-elongation-factor-1-alpha-eef1a
#16
Jędrzej Małecki, Vinay Kumar Aileni, Angela Y Y Ho, Juliane Schwarz, Anders Moen, Vigdis Sørensen, Benedikt S Nilges, Magnus E Jakobsson, Sebastian A Leidel, Pål Ø Falnes
Lysine methylation is abundant on histone proteins, representing a dynamic regulator of chromatin state and gene activity, but is also frequent on many non-histone proteins, including eukaryotic elongation factor 1 alpha (eEF1A). However, the functional significance of eEF1A methylation remains obscure and it has remained unclear whether eEF1A methylation is dynamic and subject to active regulation. We here demonstrate, using a wide range of in vitro and in vivo approaches, that the previously uncharacterized human methyltransferase METTL21B specifically targets Lys-165 in eEF1A in an aminoacyl-tRNA- and GTP-dependent manner...
January 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28103231/correction-mitochondrial-16s-rrna-is-methylated-by-trna-methyltransferase-trmt61b-in-all-vertebrates
#17
Dan Bar-Yaacov, Idan Frumkin, Yuka Yashiro, Takeshi Chujo, Yuma Ishigami, Yonatan Chemla, Amit Blumberg, Orr Schlesinger, Philipp Bieri, Basil Greber, Nenad Ban, Raz Zarivach, Lital Alfonta, Yitzhak Pilpel, Tsutomu Suzuki, Dan Mishmar
[This corrects the article DOI: 10.1371/journal.pbio.1002557.].
January 2017: PLoS Biology
https://www.readbyqxmd.com/read/28091672/a-rapid-way-to-discover-nonstandard-macrocyclic-peptide-modulators-of-drug-targets
#18
Toby Passioura, Hiroaki Suga
Studies of the fundamental nature of RNA catalysis and the potential mechanism of a shift from the "RNA world" to proteinaceous life lead us to identify a set of ribozymes (flexizymes) capable of promiscuous tRNA acylation. Whilst theoretically and mechanistically interesting in their own right, flexizymes have turned out to have immense practical value for the simple synthesis of tRNAs acylated with unusual amino acids, which in turn can be used for the ribosomal synthesis of peptides containing non-canonical residues...
January 16, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28041877/cytosine-5-rna-methylation-regulates-neural-stem-cell-differentiation-and%C3%A2-motility
#19
Joana V Flores, Lucía Cordero-Espinoza, Feride Oeztuerk-Winder, Amanda Andersson-Rolf, Tommaso Selmi, Sandra Blanco, Jignesh Tailor, Sabine Dietmann, Michaela Frye
Loss-of-function mutations in the cytosine-5 RNA methylase NSUN2 cause neurodevelopmental disorders in humans, yet the underlying cellular processes leading to the symptoms that include microcephaly remain unclear. Here, we show that NSUN2 is expressed in early neuroepithelial progenitors of the developing human brain, and its expression is gradually reduced during differentiation of human neuroepithelial stem (NES) cells in vitro. In the developing Nsun2(-/-) mouse cerebral cortex, intermediate progenitors accumulate and upper-layer neurons decrease...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/27902775/determinants-of-trna-recognition-by-the-radical-sam-enzyme-rlmn
#20
Christina M Fitzsimmons, Danica Galonić Fujimori
RlmN, a bacterial radical SAM methylating enzyme, has the unusual ability to modify two distinct types of RNA: 23S rRNA and tRNA. In rRNA, RlmN installs a methyl group at the C2 position of A2503 of 23S rRNA, while in tRNA the modification occurs at nucleotide A37, immediately adjacent to the anticodon triplet. Intriguingly, only a subset of tRNAs that contain an adenosine at position 37 are substrates for RlmN, suggesting that the enzyme carefully probes the highly conserved tRNA fold and sequence features to identify its targets...
2016: PloS One
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