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https://www.readbyqxmd.com/read/28637321/amino-acid-substrates-impose-polyamine-eif5a-or-hypusine-requirement-for-peptide-synthesis
#1
Byung-Sik Shin, Takayuki Katoh, Erik Gutierrez, Joo-Ran Kim, Hiroaki Suga, Thomas E Dever
Whereas ribosomes efficiently catalyze peptide bond synthesis by most amino acids, the imino acid proline is a poor substrate for protein synthesis. Previous studies have shown that the translation factor eIF5A and its bacterial ortholog EF-P bind in the E site of the ribosome where they contact the peptidyl-tRNA in the P site and play a critical role in promoting the synthesis of polyproline peptides. Using misacylated Pro-tRNAPhe and Phe-tRNAPro, we show that the imino acid proline and not tRNAPro imposes the primary eIF5A requirement for polyproline synthesis...
June 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28637169/novel-molecules-lncrnas-trfs-and-circrnas-deciphered-from-next-generation-sequencing-rna-sequencing-computational-databases-and-tools
#2
A Saleembhasha, Seema Mishra
Powerful next-generation sequencing (NGS) technologies, more specifically RNA sequencing (RNA-seq), have been pivotal toward the detection and analysis and hypotheses generation of novel biomolecules, long noncoding RNAs (lncRNAs), tRNA-derived fragments (tRFs) and circular RNAs (circRNAs). Experimental validation of the occurrence of these biomolecules inside the cell has been reported. Their differential expression and functionally important role in several cancers types as well as other diseases such as Alzheimer's and cardiovascular diseases have garnered interest toward further studies in this research arena...
June 20, 2017: Briefings in Functional Genomics
https://www.readbyqxmd.com/read/28636881/mitochondrial-genome-of-helice-tientsinensis-brachyura-grapsoidea-varunidae-gene-rearrangements-and-higher-level-phylogeny-of-the-brachyura
#3
Zhao-Zhe Xin, Yu-Liu, Dai-Zhen Zhang, Zheng-Fei Wang, Hua-Bin Zhang, Bo-Ping Tang, Chun-Lin Zhou, Xin-Yue Chai, Qiu-Ning Liu
The mitochondrial genome (mt genome) provides important information for understanding molecular evolution and phylogeny. The further understand the molecular evolution and phylogeny of Helice tientsinensis, the complete mt genome was determined. It is 16,212bp long and includes 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes and a control region. The genome composition of H. tientsinensis was highly A+T biased 69.0% and showed negative AT skew (-0.017) and GC skew (-0.289). One PCG, all rRNAs and 12 of the tRNAs appeared to be rearranged with respect to the pancrustacean ground pattern gene order...
June 18, 2017: Gene
https://www.readbyqxmd.com/read/28633377/emerging-mechanisms-of-aminoacyl-trna-synthetase-mutations-in-recessive-and-dominant-human-disease
#4
Rebecca Meyer-Schuman, Anthony Antonellis
Aminoacyl-tRNA synthetases (ARSs) are responsible for charging amino acids to cognate tRNA molecules, which is the essential first step of protein translation. Interestingly, mutations in genes encoding ARS enzymes have been implicated in a broad spectrum of human inherited diseases. Bi-allelic mutations in ARSs typically cause severe, early-onset, recessive diseases that affect a wide range of tissues. The vast majority of these mutations show loss-of-function effects and impair protein translation. However, it is not clear how a subset cause tissue-specific phenotypes...
June 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28632998/trna-structure-and-evolution-and-standardization-to-the-three-nucleotide-genetic-code
#5
Daewoo Pak, Robert Root-Bernstein, Zachary F Burton
Cloverleaf tRNA with a 75 nucleotide (nt) core is posited to have evolved from ligation of three 31 nt minihelices followed by symmetrical internal deletions of 9 nt within ligated acceptor stems. Statistical tests strongly support the model. Although the tRNA anticodon loop and T loop are homologs, their U-turns have been treated as distinct motifs. An appropriate comparison, however, shows that intercalation of D loop G19 between T loop bases 4 and 5 causes elevation of T loop base 5 and flipping of T loop bases 6 and 7 out of the 7 nucleotide loop...
June 20, 2017: Transcription
https://www.readbyqxmd.com/read/28632987/the-usher-syndrome-type-iiib-histidyl-trna-synthetase-mutation-confers-temperature-sensitivity
#6
Jamie A Abbott, Ethan Guth, Cindy Kim, Cathy Regan, Victoria M Siu, Charles Anthony Rupar, Borries Demeler, Christopher S Francklyn, Susan M Robey-Bond
Histidyl-tRNA synthetase (HARS) is a highly conserved translation factor that plays an essential role in protein synthesis. HARS has been implicated in the human syndromes Charcot-Marie-Tooth (CMT) Type 2W and Type IIIB Usher (USH3B). The USH3B mutation, which encodes an Y454S substitution in HARS, is inherited in an autosomal recessive fashion and associated with childhood deafness, blindness and episodic hallucinations during acute illness. The biochemical basis of the pathophysiologies linked to USH3B is currently unknown...
June 20, 2017: Biochemistry
https://www.readbyqxmd.com/read/28631407/zygote-arrest-3-that-encodes-the-trna-ligase-is-essential-for-zygote-division-in-arabidopsis
#7
Ke-Jin Yang, Lei Guo, Xiu-Li Hou, Hua-Qin Gong, Chun-Ming Liu
In sexual organisms, division of the zygote initiates a new life cycle. Although several genes involved in zygote division are known in plants, how the zygote is activated to start embryogenesis remains elusive. Here, we showed that a mutation in ZYGOTE-ARREST 3 (ZYG3) in Arabidopsis led to a tight zygote-lethal phenotype. Map-based cloning revealed that ZYG3 encodes the tRNA ligase AtRNL, which is a single-copy gene in the Arabidopsis genome. Expression analyses showed that AtRNL is expressed throughout zygotic embryogenesis, and in meristematic tissues...
June 20, 2017: Journal of Integrative Plant Biology
https://www.readbyqxmd.com/read/28630923/ribosome-rearrangements-at-the-onset-of-translational-bypassing
#8
Xabier Agirrezabala, Ekaterina Samatova, Mariia Klimova, Miguel Zamora, David Gil-Carton, Marina V Rodnina, Mikel Valle
Bypassing is a recoding event that leads to the translation of two distal open reading frames into a single polypeptide chain. We present the structure of a translating ribosome stalled at the bypassing take-off site of gene 60 of bacteriophage T4. The nascent peptide in the exit tunnel anchors the P-site peptidyl-tRNA(Gly) to the ribosome and locks an inactive conformation of the peptidyl transferase center (PTC). The mRNA forms a short dynamic hairpin in the decoding site. The ribosomal subunits adopt a rolling conformation in which the rotation of the small subunit around its long axis causes the opening of the A-site region...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28627886/experimentally-validated-model-enables-debottlenecking-of-in-vitro-protein-synthesis-and-identifies-a-control-shift-under-in-vivo-conditions
#9
Alexander Nieß, Jurek Failmezger, Maike Kuschel, Martin Siemann-Herzberg, Ralf Takors
Cell-free (in vitro) protein systems (CFPS) provide a versatile tool that can be used to investigate different aspects of the transcription-translation machinery by reducing cells to the basic functions of protein formation. Recent improvements in reaction stability and lysate preparation offer the potential to expand the scope of in vitro biosynthesis from a research tool to a multifunctional and versatile platform for protein production and synthetic biology. To date, even the best-performing CFPS are drastically slower than in vivo references...
June 19, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28626001/krs-a-cut-away-from-release-in-exosomes
#10
Catherine Rabouille
Cancer cells often trigger an inflammatory process, which in some cases may be driven by the presence of lysyl-tRNA synthetase (KRS) in the medium. Kim et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201605118) now demonstrate that cleavage of the KRS by caspase-8 inside cells triggers its interaction with syntenin and its release in inflammatory exosomes.
June 16, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28625715/discovery-of-simplified-leucyladenylate-sulfamates-as-novel-leucyl-trna-synthetase-lrs-targeted-mammalian-target-of-rapamycin-complex-1-mtorc1-inhibitors
#11
Suyoung Yoon, Jong Hyun Kim, Yura Koh, Phuong-Thao Tran, Jihyae Ann, Ina Yoon, Jayun Jang, Won Kyung Kim, Sangkook Lee, Jiyoun Lee, Sunghoon Kim, Jeewoo Lee
Leucyl-tRNA synthetase (LRS) has been reported to be a possible mediator of intracellular amino acids signaling to mTORC1. Given that mTORC1 is associated with cell proliferation and tumorigenesis, the LRS-mediated mTORC1 pathway may offer an alternative strategy in anticancer therapy. In this study, we developed a series of simplified analogues of leucyladenylate sulfamate (1) as LRS-targeted mTORC1 inhibitors. We replaced the adenylate group with a N-(3,4-dimethoxybenzyl)benzenesulfonamide (2a) or a N-(2-phenoxyethyl)benzenesulfonamide groups (2b) that can maintain specific binding, but has more favorable physicochemical properties such as reduced polarity and asymmetric centers...
June 2, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28624653/giant-ring-mitochondria-in-a-patient-with-heart-failure-and-cerebral-white-matter-disease-due-to-mt-tl1-mitochondrial-gene-mutation
#12
Brian A Houston, Daniel P Judge, Emily Brown, Marc Halushka, Lili A Barouch
BACKGROUND: The presence of giant ring mitochondria on endomyocardial biopsy is rarely reported and does not have a well-defined differential diagnosis. METHODS: We report the case of a 54-year-old man with heart failure with preserved ejection fraction and left ventricular hypertrophy, initially thought to have an infiltrative cardiomyopathy. RESULTS: The patient was found to have extensive vacuolization caused by the presence of giant ring mitochondria on endomyocardial biopsy...
June 14, 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28623884/mitochondrial-rna-processing-in-absence-of-trna-punctuations-in-octocorals
#13
Gaurav G Shimpi, Sergio Vargas, Angelo Poliseno, Gert Wörheide
BACKGROUND: Mitogenome diversity is staggering among early branching animals with respect to size, gene density, content and order, and number of tRNA genes, especially in cnidarians. This last point is of special interest as tRNA cleavage drives the maturation of mitochondrial mRNAs and is a primary mechanism for mt-RNA processing in animals. Mitochondrial RNA processing in non-bilaterian metazoans, some of which possess a single tRNA gene in their mitogenomes, is essentially unstudied despite its importance in understanding the evolution of mitochondrial transcription in animals...
June 17, 2017: BMC Molecular Biology
https://www.readbyqxmd.com/read/28623126/crystal-structure-of-trna-his-guanylyltransferase-from-saccharomyces-cerevisiae
#14
Kitaik Lee, Eun Hye Lee, Jonghyeon Son, Kwang Yeon Hwang
tRNA maturation involves several steps, including processing, splicing, CCA addition, and posttranscriptional modifications. tRNA(His) guanylyltransferase (Thg1) is the only enzyme known to catalyze templated nucleotide addition in the 3'-5' direction, unlike other DNA and RNA polymerases. For a better understanding of its unique catalytic mechanism at the molecular level, we determined the crystal structure of GTP-bound Thg1 from Saccharomyces cerevisiae at the maximum resolution of 3.0 Å. The structure revealed the enzyme to have a tetrameric conformation that is well conserved among different species, and the GTP molecule was clearly bound at the active site, coordinating with two magnesium ions...
June 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28622362/the-complete-mitochondrial-genome-of-sesarmops-sinensis-reveals-gene-rearrangements-and-phylogenetic-relationships-in-brachyura
#15
Bo-Ping Tang, Zhao-Zhe Xin, Yu Liu, Dai-Zhen Zhang, Zheng-Fei Wang, Hua-Bin Zhang, Xin-Yue Chai, Chun-Lin Zhou, Qiu-Ning Liu
Mitochondrial genome (mitogenome) is very important to understand molecular evolution and phylogenetics. Herein, in this study, the complete mitogenome of Sesarmops sinensis was reported. The mitogenome was 15,905 bp in size, and contained 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a control region (CR). The AT skew and the GC skew are both negative in the mitogenomes of S. sinensis. The nucleotide composition of the S. sinensis mitogenome was also biased toward A + T nucleotides (75...
2017: PloS One
https://www.readbyqxmd.com/read/28621923/capture-and-release-of-trna-by-the-t-loop-receptor-in-the-function-of-the-t-box-riboswitch
#16
Xianyang Fang, Malgorzata Michnicka, Yikan Zhang, Yun Xing Wang, Edward P Nikonowicz
In Gram-positive bacteria, the tRNA-dependent T-box riboswitch system regulates expression of amino acid biosynthetic and aminoacyl-tRNA synthetase genes through a transcription attenuation mechanism. Binding of uncharged tRNA "closes" the switch, allowing transcription read-through. Structure studies of the 100 nt stem I domain reveal tRNA utilizes base pairing and stacking interactions to bind the stem, but little is known structurally about the 180 nt riboswitch core (stem I, stem III, and antiterminator stem) in complex with tRNA and the mechanism of coupling of the intermolecular binding domains crucial to T-box function...
June 16, 2017: Biochemistry
https://www.readbyqxmd.com/read/28620870/severe-growth-deficiency-microcephaly-intellectual-disability-and-characteristic-facial-features-are-due-to-a-homozygous-qars-mutation
#17
Esther Leshinsky-Silver, Jiqiang Ling, Jiang Wu, Chana Vinkler, Keren Yosovich, Sarit Bahar, Miri Yanoov-Sharav, Tally Lerman-Sagie, Dorit Lev
Glutaminyl tRNA synthase is highly expressed in the developing fetal human brain. Mutations in the glutaminyl-tRNA synthetase (QARS) gene have been reported in patients with progressive microcephaly, cerebral-cerebellar atrophy, and intractable seizures. We have previously reported a new recessive syndrome of severe linear growth retardation, poor weight gain, microcephaly, characteristic facial features, cutaneous syndactyly of the toes, high myopia, and intellectual disability in two sisters of Ashkenazi-Jewish origin (Eur J Med Genet 2014;57(6):288-92)...
June 15, 2017: Neurogenetics
https://www.readbyqxmd.com/read/28620368/an-arod-ochre-mutation-results-in-a-staphylococcus-aureus-small-colony-variant-that-can-undergo-phenotypic-switching-via-two-alternative-mechanisms
#18
Ping Zhang, John A Wright, Ahmed A Osman, Sean P Nair
Staphylococcus aureus can undergo phenotypic switching between a normal colony phenotype (NCP) and a small colony variant (SCV). The SCV phenotype confers increased antibiotic resistance and the capacity to persist within human tissues and cells, and because these cells can revert back to the NCP they cause chronic and/or recurrent infections that are very difficult to treat. A complete picture of the genetic events that can lead to phenotypic switching in S. aureus is currently lacking. We describe the selection of an SCV with a previously unreported genetic alteration leading to an ochre mutation of aroD...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28619807/genome-sequence-of-prosthecochloris-sp-strain-hl-130-gsb-from-the-phylum-chlorobi
#19
Vera Thiel, Daniela I Drautz-Moses, Rikky W Purbojati, Stephan C Schuster, Stephen Lindemann, Donald A Bryant
The genome of the green sulfur bacterium Prosthecochloris sp. strain HL-130-GSB, isolated from a cyanobacterial mat obtained from Hot Lake, a saline meromictic lake in Washington, USA, comprises 2,437,774 bp in a single contig. The genome is predicted to encode 2,565 proteins and contain 47 tRNA genes and 2 rRNA operons.
June 15, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28617965/further-delineation-of-the-phenotype-caused-by-biallelic-variants-in-the-wdr4-gene
#20
Aurélien Trimouille, Eulalie Lasseaux, Pascal Barat, Caroline Deiller, Séverine Drunat, Caroline Rooryck, Benoît Arveiler, Didier Lacombe
Microcephalic primordial dwarfisms are a group of rare Mendelian disorders characterized by severe growth retardation and microcephaly. The molecular basis is heterogeneous, with disease-causing genes implicated in different cellular functions. Recently, 2 patients were reported with the same homozygous variant in the WDR4 gene, coding for an enzyme responsible for the m(7) G46 post transcriptional modification of tRNA. We report here two sisters harboring compound heterozygous variants of WDR4. Their phenotype differs from that of the first two described patients: they both have a severe microcephaly but only one of the two sisters had a head circumference at birth below -2 SD, their intellectual deficiency is less severe, and they have a GH deficiency and a partial hypogonadotropic hypogonadotropism...
June 15, 2017: Clinical Genetics
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