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tRNA methylation

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https://www.readbyqxmd.com/read/27902775/determinants-of-trna-recognition-by-the-radical-sam-enzyme-rlmn
#1
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
https://www.readbyqxmd.com/read/27870114/the-molecular-genetics-of-autosomal-recessive-nonsyndromic-intellectual-disability-a-mutational-continuum-and-future-recommendations
#2
REVIEW
Muzammil Ahmad Khan, Saadullah Khan, Christian Windpassinger, Muhammad Badar, Zafar Nawaz, Ramzi M Mohammad
Intellectual disability (ID) is a clinical manifestation of the central nervous system without any major dysmorphologies of the brain. Biologically it affects learning capabilities, memory, and cognitive functioning. The basic defining features of ID are characterized by IQ<70, age of onset before 18 years, and impairment of at least two of the adaptive skills. Clinically it is classified in a syndromic (with additional abnormalities) and a nonsyndromic form (with only cognitive impairment). The study of nonsyndromic intellectual disability (NSID) can best explain the pathophysiology of cognition, intelligence and memory...
November 2016: Annals of Human Genetics
https://www.readbyqxmd.com/read/27852927/evolution-of-trnaphe-img2-methyltransferases-involved-in-the-biosynthesis-of-wyosine-derivatives-in-archaea
#3
Jaunius Urbonavičius, Rasa Rutkienė, Anželika Lopato, Daiva Tauraitė, Jonita Stankevičiūtė, Agota Aučynaitė, Laura Kaliniene, Herman van Tilbeurgh, Rolandas Meškys
Tricyclic wyosine derivatives are found at position 37 of eukaryotic and archaeal tRNA(Phe) In Archaea, the intermediate imG-14 is targeted by three different enzymes that catalyze the formation of yW-86, imG, and imG2. We have suggested previously that a peculiar methyltransferase (aTrm5a/Taw22) likely catalyzes two distinct reactions: N(1)-methylation of guanosine to yield m(1)G; and C(7)-methylation of imG-14 to yield imG2. Here we show that the recombinant aTrm5a/Taw22-like enzymes from both Pyrococcus abyssi and Nanoarchaeum equitans indeed possess such dual specificity...
December 2016: RNA
https://www.readbyqxmd.com/read/27849575/mg2-regulates-transcription-of-mgta-in-salmonella-typhimurium-via-translation-of-proline-codons-during-synthesis-of-the-mgtl-peptide
#4
Aaron R Gall, Kirill A Datsenko, Nara Figueroa-Bossi, Lionello Bossi, Isao Masuda, Ya-Ming Hou, Laszlo N Csonka
In Salmonella enterica serovar Typhimurium, Mg(2+) limitation induces transcription of the mgtA Mg(2+) transport gene, but the mechanism involved is unclear. The 5' leader of the mgtA mRNA contains a 17-codon, proline-rich ORF, mgtL, whose translation regulates the transcription of mgtA [Park S-Y et al. (2010) Cell 142:737-748]. Rapid translation of mgtL promotes formation of a secondary structure in the mgtA mRNA that permits termination of transcription by the Rho protein upstream of mgtA, whereas slow or incomplete translation of mgtL generates a different structure that blocks termination...
November 14, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27819523/the-rna-methyltransferase-dnmt2-methylates-dna-in-the-structural-context-of-a-trna
#5
Steffen Kaiser, Tomasz P Jurkowski, Stefanie Kellner, Dirk Schneider, Albert Jeltsch, Mark Helm
The amino acid sequence of Dnmt2 is very similar to the catalytic domains of bacterial and eukaryotic DNA-(cytosine 5)-methyltransferases, but it efficiently catalyzes tRNA methylation, while its DNA methyltransferase activity is the subject of controversial reports with rates varying between zero and very weak. By using composite nucleic acid molecules as substrates, we surprisingly found that DNA fragments, when presented as covalent DNA-RNA hybrids in the structural context of a tRNA, can be more efficiently methylated than the corresponding natural tRNA substrate...
November 7, 2016: RNA Biology
https://www.readbyqxmd.com/read/27805064/comprehensive-dna-methylation-analysis-of-the-aedes-aegypti-genome
#6
Cassandra Falckenhayn, Vitor Coutinho Carneiro, Anderson de Mendonça Amarante, Katharina Schmid, Katharina Hanna, Seokyoung Kang, Mark Helm, George Dimopoulos, Marcelo Rosado Fantappié, Frank Lyko
Aedes aegypti mosquitoes are important vectors of viral diseases. Mosquito host factors play key roles in virus control and it has been suggested that dengue virus replication is regulated by Dnmt2-mediated DNA methylation. However, recent studies have shown that Dnmt2 is a tRNA methyltransferase and that Dnmt2-dependent methylomes lack defined DNA methylation patterns, thus necessitating a systematic re-evaluation of the mosquito genome methylation status. We have now searched the Ae. aegypti genome for candidate DNA modification enzymes...
November 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27791159/avilamycin-and-evernimicin-induce-structural-changes-in-rproteins-ul16-and-ctc-that-enhance-the-inhibition-of-a-site-trna-binding
#7
Miri Krupkin, Itai Wekselman, Donna Matzov, Zohar Eyal, Yael Diskin Posner, Haim Rozenberg, Ella Zimmerman, Anat Bashan, Ada Yonath
Two structurally unique ribosomal antibiotics belonging to the orthosomycin family, avilamycin and evernimicin, possess activity against Enterococci, Staphylococci, and Streptococci, and other Gram-positive bacteria. Here, we describe the high-resolution crystal structures of the eubacterial large ribosomal subunit in complex with them. Their extended binding sites span the A-tRNA entrance corridor, thus inhibiting protein biosynthesis by blocking the binding site of the A-tRNA elbow, a mechanism not shared with other known antibiotics...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27769719/analysis-of-the-cleavage-mechanism-by-protein-only-rnase-p-using-precursor-trna-substrates-with-modifications-at-the-cleavage-site
#8
Dennis Walczyk, Markus Gößringer, Walter Rossmanith, Timofei S Zatsepin, Tatiana S Oretskaya, Roland K Hartmann
Ribonuclease P (RNase P) is the enzyme that endonucleolytically removes 5'-precursor sequences from tRNA transcripts in all domains of life. RNase P activities are either ribonucleoprotein (RNP) or protein-only (PRORP) enzymes, raising the question about the mechanistic strategies utilized by these architecturally different enzyme classes to catalyze the same type of reaction. Here we analyzed the kinetics and cleavage-site selection by PRORP3 from Arabidopsis thaliana (AtPRORP3) using precursor tRNAs (pre-tRNAs) with individual modifications at the canonical cleavage site, either Rp- or Sp-phosphorothioate, or 2'-deoxy, 2'-fluoro, 2'-amino or 2'-O-methyl substitutions...
October 18, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27765658/occupational-exposures-at-a-polyvinyl-chloride-production-facility-are-associated-with-significant-changes-to-the-plasma-metabolome
#9
John J Guardiola, Juliane I Beier, K Cameron Falkner, Benjamin Wheeler, Craig James McClain, Matt Cave
BACKGROUND: Occupational vinyl chloride (VC) exposures have been associated with toxicant-associated steatohepatitis and liver cancer. Metabolomics has been used to clarify mode of action in drug-induced liver injury but has not been performed following VC exposures. METHODS: Plasma samples from 17 highly exposed VC workers without liver cancer and 27 unexposed healthy volunteers were obtained for metabolite extraction and GC/MS and LC/MS(2) analysis. Following ion identification/quantification, Ingenuity pathway analysis was performed...
December 15, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27745969/alkbh1-mediated-trna-demethylation-regulates-translation
#10
Fange Liu, Wesley Clark, Guanzheng Luo, Xiaoyun Wang, Ye Fu, Jiangbo Wei, Xiao Wang, Ziyang Hao, Qing Dai, Guanqun Zheng, Honghui Ma, Dali Han, Molly Evans, Arne Klungland, Tao Pan, Chuan He
tRNA is a central component of protein synthesis and the cell signaling network. One salient feature of tRNA is its heavily modified status, which can critically impact its function. Here, we show that mammalian ALKBH1 is a tRNA demethylase. It mediates the demethylation of N(1)-methyladenosine (m(1)A) in tRNAs. The ALKBH1-catalyzed demethylation of the target tRNAs results in attenuated translation initiation and decreased usage of tRNAs in protein synthesis. This process is dynamic and responds to glucose availability to affect translation...
October 20, 2016: Cell
https://www.readbyqxmd.com/read/27703015/sequence-specific-and-shape-selective-rna-recognition-by-the-human-rna-5-methylcytosine-methyltransferase-nsun6
#11
Tao Long, Jing Li, Hao Li, Mi Zhou, Xiao-Long Zhou, Ru-Juan Liu, En-Duo Wang
Human NSun6 is an RNA methyltransferase that catalyzes the transfer of the methyl group from S-adenosyl-l-methionine (SAM) to C72 of tRNA(Thr) and tRNA(Cys) In the current study, we used mass spectrometry to demonstrate that human NSun6 indeed introduces 5-methylcytosine (m(5)C) into tRNA, as expected. To further reveal the tRNA recognition mechanism of human NSun6, we measured the methylation activity of human NSun6 and its kinetic parameters for different tRNA substrates and their mutants. We showed that human NSun6 requires a well folded, full-length tRNA as its substrate...
November 11, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27683218/methylation-at-position-32-of-trna-catalyzed-by-trmj-alters-oxidative-stress-response-in-pseudomonas-aeruginosa
#12
Juthamas Jaroensuk, Sopapan Atichartpongkul, Yok Hian Chionh, Yee Hwa Wong, Chong Wai Liew, Megan E McBee, Narumon Thongdee, Erin G Prestwich, Michael S DeMott, Skorn Mongkolsuk, Peter C Dedon, Julien Lescar, Mayuree Fuangthong
Bacteria respond to environmental stresses using a variety of signaling and gene expression pathways, with translational mechanisms being the least well understood. Here, we identified a tRNA methyltransferase in Pseudomonas aeruginosa PA14, trmJ, which confers resistance to oxidative stress. Analysis of tRNA from a trmJ mutant revealed that TrmJ catalyzes formation of Cm, Um, and, unexpectedly, Am. Defined in vitro analyses revealed that tRNA(Met(CAU)) and tRNA(Trp(CCA)) are substrates for Cm formation, tRNA(Gln(UUG)), tRNA(Pro(UGG)), tRNA(Pro(CGG)) and tRNA(His(GUG)) for Um, and tRNA(Pro(GGG)) for Am...
September 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27681416/uniformity-of-peptide-release-is-maintained-by-methylation-of-release-factors
#13
William E Pierson, Eric D Hoffer, Hannah E Keedy, Carrie L Simms, Christine M Dunham, Hani S Zaher
Termination of protein synthesis on the ribosome is catalyzed by release factors (RFs), which share a conserved glycine-glycine-glutamine (GGQ) motif. The glutamine residue is methylated in vivo, but a mechanistic understanding of its contribution to hydrolysis is lacking. Here, we show that the modification, apart from increasing the overall rate of termination on all dipeptides, substantially increases the rate of peptide release on a subset of amino acids. In the presence of unmethylated RFs, we measure rates of hydrolysis that are exceptionally slow on proline and glycine residues and approximately two orders of magnitude faster in the presence of the methylated factors...
September 27, 2016: Cell Reports
https://www.readbyqxmd.com/read/27679614/new-insight-into-isoprenoids-biosynthesis-process-and-future-prospects-for-drug-designing-in-plasmodium
#14
REVIEW
Gagandeep S Saggu, Zarna R Pala, Shilpi Garg, Vishal Saxena
The MEP (Methyl Erythritol Phosphate) isoprenoids biosynthesis pathway is an attractive drug target to combat malaria, due to its uniqueness and indispensability for the parasite. It is functional in the apicoplast of Plasmodium and its products get transported to the cytoplasm, where they participate in glycoprotein synthesis, electron transport chain, tRNA modification and several other biological processes. Several compounds have been tested against the enzymes involved in this pathway and amongst them Fosmidomycin, targeted against IspC (DXP reductoisomerase) enzyme and MMV008138 targeted against IspD enzyme have shown good anti-malarial activity in parasite cultures...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27647777/reassigning-sense-codon-aga-to-encode-noncanonical-amino-acids-in-escherichia-coli
#15
Yiyan Wang, Meng-Lin Tsao
A new method has been developed to reassign the rare codon AGA in Escherichia coli by engineering an orthogonal tRNA/aminoacyl-tRNA synthetase pair derived from Methanocaldococcus jannaschii. The tRNA mutant was introduced with a UCU anticodon, and the synthetase was evolved to correctly recognize the modified tRNA anticodon loop and to selectively charge a target noncanonical amino acid (NAA) onto the tRNA. In order to maximize the efficiency of AGA codon reassignment, while avoiding the lethal effects caused by global codon reassignment in cellular proteins, an inducible promoter (araBAD) was utilized to provide temporal controls for overexpression of the aminoacyl-tRNA synthetase and switch on codon reassignment...
September 20, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27631568/mitochondrial-16s-rrna-is-methylated-by-trna-methyltransferase-trmt61b-in-all-vertebrates
#16
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
The mitochondrial ribosome, which translates all mitochondrial DNA (mtDNA)-encoded proteins, should be tightly regulated pre- and post-transcriptionally. Recently, we found RNA-DNA differences (RDDs) at human mitochondrial 16S (large) rRNA position 947 that were indicative of post-transcriptional modification. Here, we show that these 16S rRNA RDDs result from a 1-methyladenosine (m1A) modification introduced by TRMT61B, thus being the first vertebrate methyltransferase that modifies both tRNA and rRNAs. m1A947 is conserved in humans and all vertebrates having adenine at the corresponding mtDNA position (90% of vertebrates)...
September 2016: PLoS Biology
https://www.readbyqxmd.com/read/27629654/crystal-structures-of-the-bifunctional-trna-methyltransferase-trm5a
#17
Caiyan Wang, Qian Jia, Ran Chen, Yuming Wei, Juntao Li, Jie Ma, Wei Xie
tRNA methyltransferase Trm5 catalyses the transfer of a methyl group from S-adenosyl-L-methionine to G37 in eukaryotes and archaea. The N1-methylated guanosine is the product of the initial step of the wyosine hypermodification, which is essential for the maintenance of the reading frame during translation. As a unique member of this enzyme family, Trm5a from Pyrococcus abyssi (PaTrm5a) catalyses not only the methylation of N1, but also the further methylation of C7 on 4-demethylwyosine at position 37 to produce isowyosine, but the mechanism for the double methylation is poorly understood...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27613580/trna-base-methylation-identification-and-quantification-via-high-throughput-sequencing
#18
Wesley C Clark, Molly E Evans, Dan Dominissini, Guanqun Zheng, Tao Pan
Eukaryotic transfer RNAs contain on average 14 modifications. Investigations of their biological functions require the determination of the modification sites and the dynamic variations of the modification fraction. Base methylation represents a major class of tRNA modification. Although many approaches have been used to identify tRNA base methylations, including sequencing, they are generally qualitative and do not report the information on the modification fraction. Dynamic mRNA modifications have been shown to play important biological roles; yet, the extent of tRNA modification fractions has not been reported systemically...
November 2016: RNA
https://www.readbyqxmd.com/read/27582183/crystal-structure-of-the-two-subunit-trna-m-1-a58-methyltransferase-trm6-trm61-from-saccharomyces-cerevisiae
#19
Mingxing Wang, Yuwei Zhu, Chongyuan Wang, Xiaojiao Fan, Xuguang Jiang, Mohammad Ebrahimi, Zhi Qiao, Liwen Niu, Maikun Teng, Xu Li
The N(1) methylation of adenine at position 58 (m(1)A58) of tRNA is an important post-transcriptional modification, which is vital for maintaining the stability of the initiator methionine tRNAi(Met). In eukaryotes, this modification is performed by the TRM6-TRM61 holoenzyme. To understand the molecular mechanism that underlies the cooperation of TRM6 and TRM61 in the methyl transfer reaction, we determined the crystal structure of TRM6-TRM61 holoenzyme from Saccharomyces cerevisiae in the presence and absence of its methyl donor S-Adenosyl-L-methionine (SAM)...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27571175/methyl-transfer-by-substrate-signaling-from-a-knotted-protein-fold
#20
Thomas Christian, Reiko Sakaguchi, Agata P Perlinska, Georges Lahoud, Takuhiro Ito, Erika A Taylor, Shigeyuki Yokoyama, Joanna I Sulkowska, Ya-Ming Hou
Proteins with knotted configurations, in comparison with unknotted proteins, are restricted in conformational space. Little is known regarding whether knotted proteins have sufficient dynamics to communicate between spatially separated substrate-binding sites. TrmD is a bacterial methyltransferase that uses a knotted protein fold to catalyze methyl transfer from S-adenosyl methionine (AdoMet) to G37-tRNA. The product, m(1)G37-tRNA, is essential for life and maintains protein-synthesis reading frames. Using an integrated approach of structural, kinetic, and computational analysis, we show that the structurally constrained TrmD knot is required for its catalytic activity...
October 2016: Nature Structural & Molecular Biology
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