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tRNA methylation

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https://www.readbyqxmd.com/read/28418649/nature-s-selection-of-geranyl-group-as-a-trna-modification-the-effects-of-chain-length-on-base-pairing-specificity
#1
Phensinee Haruehanroengra, Sweta Vangaveti, Srivathsan V Ranganathan, Rui Wang, Alan Chen, Jia Sheng
The recently discovered geranyl modification on the 2-thio position of wobble U34 residues in tRNA(Glu), tRNA(Lys), and tRNA(Gln) in several bacteria has been found to enhance the U:G pairing specificity and reduce the frameshifting error during translation. It is a fundamentally interesting question why nature chose a C10 terpene group in tRNA systems. In this study, we explore the significance of the terpene length on base-paring stability and specificity using a series of 2-thiouridine analogues containing different lengths of carbon chains, namely, methyl- (C1), dimethylallyl- (C5), and farnesyl-modified (C15) 2-thiothymidines in a DNA duplex...
April 18, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28371071/selective-enzymatic-demethylation-of-n-2-n-2-dimethylguanosine-in-rna-and-its-application-in-high-throughput-trna-sequencing
#2
Qing Dai, Guanqun Zheng, Michael H Schwartz, Wesley C Clark, Tao Pan
The abundant Watson-Crick face methylations in biological RNAs such as N(1) -methyladenosine (m(1) A), N(1) -methylguanosine (m(1) G), N(3) -methylcytosine (m(3) C), and N(2) ,N(2) -dimethylguanosine (m(2)2 G) cause significant obstacles for high-throughput RNA sequencing by impairing cDNA synthesis. One strategy to overcome this obstacle is to remove the methyl group on these modified bases prior to cDNA synthesis using enzymes. The wild-type E. coli AlkB and its D135S mutant can remove most of m(1) A, m(1) G, m(3) C modifications in transfer RNA (tRNA), but they work poorly on m(2)2 G...
March 30, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28357324/sulfur-transfer-and-activation-by-ubiquitin-like-modifier-system-uba4%C3%A2-urm1-link-protein-urmylation-and-trna-thiolation-in-yeast
#3
André Jüdes, Alexander Bruch, Roland Klassen, Mark Helm, Raffael Schaffrath
Urm1 is a unique dual-function member of the ubiquitin protein family and conserved from yeast to man. It acts both as a protein modifier in ubiquitin-like urmylation and as a sulfur donor for tRNA thiolation, which in concert with the Elongator pathway forms 5-methoxy-carbonyl-methyl-2-thio (mcm(5)s(2)) modified wobble uridines (U34) in anticodons. Using Saccharomyces cerevisiae as a model to study a relationship between these two functions, we examined whether cultivation temperature and sulfur supply previously implicated in the tRNA thiolation branch of the URM1 pathway also contribute to proper urmylation...
October 24, 2016: Microbial Cell
https://www.readbyqxmd.com/read/28349464/high-throughput-small-rna-sequencing-enhanced-by-alkb-facilitated-rna-de-methylation-arm-seq
#4
Eva Hrabeta-Robinson, Erin Marcus, Aaron E Cozen, Eric M Phizicky, Todd M Lowe
N (1)-methyladenosine (m(1)A), N (3)-methylcytidine (m(3)C), and N (1)-methylguanosine (m(1)G) are common in transfer RNA (tRNA) and tRNA-derived fragments. These modifications alter Watson-Crick base-pairing, and cause pauses or stops during reverse transcription required for most high-throughput RNA sequencing protocols, resulting in inefficient detection of methyl-modified RNAs. Here, we describe a procedure to demethylate RNAs containing m(1)A, m(3)C, or m(1)G using the Escherichia coli dealkylating enzyme AlkB, along with instructions for subsequent processing with widely used protocols for small RNA sequencing...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28349451/comparative-analysis-of-ribonucleic-acid-digests-card-by-mass-spectrometry
#5
Mellie June Paulines, Patrick A Limbach
We describe the comparative analysis of ribonucleic acid digests (CARD) approach for RNA modification analysis. This approach employs isotope labeling during RNase digestion, which allows the direct comparison of a tRNA of unknown modification status against a reference tRNA, whose sequence or modification status is known. The reference sample is labeled with (18)O during RNase digestion while the candidate (unknown) sample is labeled with (16)O. These RNase digestion products are combined and analyzed by mass spectrometry...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28335556/trm5-and-trmd-two-enzymes-from-distinct-origins-catalyze-the-identical-trna-modification-m%C3%A2-g37
#6
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-homologue-1-alkbh1
#7
Tina A Müller, Michael A Tobar, Madison N Perian, Robert P Hausinger
Alkbh1 is one of nine mammalian homologues 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 of two of these enzymatic activities using human ALKBH1: the AP lyase and 6-methyl adenine DNA demethylase activities...
April 4, 2017: Biochemistry
https://www.readbyqxmd.com/read/28281930/combined-trna-modification-defects-impair-protein-homeostasis-and-synthesis-of-the-yeast-prion-protein-rnq1
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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