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https://www.readbyqxmd.com/read/29235198/substrate-interaction-defects-in-histidyl-trna-synthetase-linked-to-dominant-axonal-peripheral-neuropathy
#1
Jamie A Abbott, Rebecca Meyer-Schuman, Vincenzo Lupo, Shawna Feely, Inès Mademan, Stephanie N Oprescu, Laurie B Griffin, M Antonia Alberti, Carlos Casasnovas, Sharon Aharoni, Lina Basel-Vanagaite, Stephan Züchner, Peter De Jonghe, Jonathan Baets, Michael E Shy, Carmen Espinós, Borries Demeler, Anthony Antonellis, Christopher Francklyn
Histidyl-tRNA synthetase (HARS) ligates histidine to cognate tRNA molecules, which is required for protein translation. Mutations in HARS cause the dominant axonal peripheral neuropathy Charcot Marie-Tooth disease type 2W (CMT2W); however, the precise molecular mechanism remains undefined. Here, we investigated three HARS missense mutations associated with CMT2W (p.Tyr330Cys, p.Ser356Asn, and p.Val155Gly). The three mutations localize to the HARS catalytic domain and failed to complement deletion of the yeast ortholog (HTS1)...
December 12, 2017: Human Mutation
https://www.readbyqxmd.com/read/29233224/ribosome-structural-dynamics-in-translocation-yet-another-functional-role-for-ribosomal-rna
#2
Harry F Noller, Laura Lancaster, Srividya Mohan, Jie Zhou
Ribosomes are remarkable ribonucleoprotein complexes that are responsible for protein synthesis in all forms of life. They polymerize polypeptide chains programmed by nucleotide sequences in messenger RNA in a mechanism mediated by transfer RNA. One of the most challenging problems in the ribosome field is to understand the mechanism of coupled translocation of mRNA and tRNA during the elongation phase of protein synthesis. In recent years, the results of structural, biophysical and biochemical studies have provided extensive evidence that translocation is based on the structural dynamics of the ribosome itself...
January 2017: Quarterly Reviews of Biophysics
https://www.readbyqxmd.com/read/29232904/an-expanded-multi-organ-disease-phenotype-associated-with-mutations-in-yars
#3
Anna Tracewska-Siemiątkowska, Lonneke Haer-Wigman, Danielle G M Bosch, Deborah Nickerson, Michael J Bamshad, Maartje van de Vorst, Nanna Dahl Rendtorff, Claes Möller, Ulrika Kjellström, Sten Andréasson, Frans P M Cremers, Lisbeth Tranebjærg
Whole exome sequence analysis was performed in a Swedish mother-father-affected proband trio with a phenotype characterized by progressive retinal degeneration with congenital nystagmus, profound congenital hearing impairment, primary amenorrhea, agenesis of the corpus callosum, and liver disease. A homozygous variant c.806T > C, p.(F269S) in the tyrosyl-tRNA synthetase gene (YARS) was the only identified candidate variant consistent with autosomal recessive inheritance. Mutations in YARS have previously been associated with both autosomal dominant Charcot-Marie-Tooth syndrome and a recently reported autosomal recessive multiorgan disease...
December 11, 2017: Genes
https://www.readbyqxmd.com/read/29229848/three-trnas-on-the-ribosome-slow-translation-elongation
#4
Junhong Choi, Joseph D Puglisi
During protein synthesis, the ribosome simultaneously binds up to three different transfer RNA (tRNA) molecules. Among the three tRNA binding sites, the regulatory role of the exit (E) site, where deacylated tRNA spontaneously dissociates from the translational complex, has remained elusive. Here we use two donor-quencher pairs to observe and correlate both the conformation of ribosomes and tRNAs as well as tRNA occupancy. Our results reveal a partially rotated state of the ribosome wherein all three tRNA sites are occupied during translation elongation...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29229607/race-disparities-in-the-contribution-of-mirna-isoforms-and-trna-derived-fragments-to-triple-negative-breast-cancer
#5
Aristeidis G Telonis, Isidore Rigoutsos
Triple-Negative Breast Cancer (TNBC) is a breast cancer subtype characterized by marked differences between White and Black/African-American women. We performed a systems-level analysis on datasets from The Cancer Genome Atlas (TCGA) to elucidate how the expression patterns of messenger RNAs (mRNAs) are shaped by regulatory non-coding RNAs (ncRNAs). Specifically, we studied isomiRs, i.e. isoforms of microRNAs (miRNAs), and tRNA-derived fragments (tRFs). In normal breast tissue, we observed a marked cohesiveness in both the ncRNA and mRNA layers and the associations between them...
December 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/29229096/clinical-characteristics-of-patients-with-anti-aminoacyl-trna-synthetase-antibody-positive-idiopathic-interstitial-pneumonia
#6
Hirokazu Yura, Noriho Sakamoto, Minoru Satoh, Hiroshi Ishimoto, Tetsuya Hanaka, Chiyo Ito, Tomoko Hasegawa, Shin Tanaka, Takuto Miyamura, Shota Nakashima, Atsuko Hara, Tomoyuki Kakugawa, Keishi Oda, Takashi Kido, Yasushi Obase, Yuji Ishimatsu, Kazuhiro Yatera, Atsushi Kawakami, Hiroshi Mukae
BACKGROUND: Anti-aminoacyl-tRNA synthetase (ARS) antibodies have been detected in patients with polymyositis/dermatomyositis (PM/DM) and are especially correlated with interstitial lung disease (ILD). The aim of this study was to clarify the clinical features of patients with anti-ARS antibody positive idiopathic interstitial pneumonias (IIPs). METHODS: Patients were classified into three groups: 1) IIP with anti-ARS antibodies (ARS(+)IIP), 2) IIP without anti-ARS antibodies (ARS(-)IIP), and 3) PM/DM-associated ILD with anti-ARS antibodies (ARS(+)PM/DM-ILD)...
November 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/29228294/accurate-mapping-of-trna-reads
#7
Anne Hoffmann, Jörg Fallmann, Mario Mörl, Peter F Stadler, Fabian Amman
Motivation: Many repetitive DNA elements are transcribed at appreciable expression levels. Mapping the corresponding RNA sequencing reads back to a reference genome is notoriously difficult and error-prone task, however. This is in particular true if chemical modifications introduce systematic mismatches, while at the same time the genomic loci are only approximately identical, as in the case of tRNAs. Results: We therefore developed a dedicated mapping strategy to handle RNA-seq reads that map to tRNAs relying on a modified target genome in which known tRNA loci are masked and instead intronless tRNA precursor sequences are appended as artificial "chromosomes"...
December 8, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29228266/editing-activity-for-eliminating-mischarged-trnas-is-essential-in-mammalian-mitochondria
#8
Taru Hilander, Xiao-Long Zhou, Svetlana Konovalova, Fu-Ping Zhang, Liliya Euro, Dmitri Chilov, Matti Poutanen, Joseph Chihade, En-Duo Wang, Henna Tyynismaa
Accuracy of protein synthesis is enabled by the selection of amino acids for tRNA charging by aminoacyl-tRNA synthetases (ARSs), and further enhanced by the proofreading functions of some of these enzymes for eliminating tRNAs mischarged with noncognate amino acids. Mouse models of editing-defective cytoplasmic alanyl-tRNA synthetase (AlaRS) have previously demonstrated the importance of proofreading for cytoplasmic protein synthesis, with embryonic lethal and progressive neurodegeneration phenotypes. Mammalian mitochondria import their own set of nuclear-encoded ARSs for translating critical polypeptides of the oxidative phosphorylation system, but the importance of editing by the mitochondrial ARSs for mitochondrial proteostasis has not been known...
December 8, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29227991/predicting-the-pathogenicity-of-novel-variants-in-mitochondrial-trna-with-mitotip
#9
Sanjay Sonney, Jeremy Leipzig, Marie T Lott, Shiping Zhang, Vincent Procaccio, Douglas C Wallace, Neal Sondheimer
Novel or rare variants in mitochondrial tRNA sequences may be observed after mitochondrial DNA analysis. Determining whether these variants are pathogenic is critical, but confirmation of the effect of a variant on mitochondrial function can be challenging. We have used available databases of benign and pathogenic variants, alignment between diverse tRNAs, structural information and comparative genomics to predict the impact of all possible single-base variants and deletions. The Mitochondrial tRNA Informatics Predictor (MitoTIP) is available through MITOMAP at www...
December 11, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29225267/a-rare-combination-of-dermatomyositis-interstitial-pneumonia-and-lung-cancer-in-a-patient-treated-with-immunosuppressive-therapy-and-chemotherapy-a-case-report
#10
Wakako Daido, Masahiro Yamasaki, Yuka Morio, Kunihiko Funaishi, Sayaka Ishiyama, Naoko Deguchi, Masaya Taniwaki, Nobuyuki Ohashi, Noboru Hattori
We herein report the rare case of co-occurring dermatomyositis (DM), interstitial pneumonia (IP), and lung cancer in a 59-year-old man. Computed tomography (CT) and positron emission tomography-CT showed the presence of a left lung tumor with IP, which was diagnosed as lung adenocarcinoma by a CT-guided tumor biopsy. We diagnosed DM based on the presence of myalgia, Gottron's papules, and anti-aminoacyl-tRNA synthetase antibody positivity in the patient. Co-occurrence of the above-mentioned three diseases is rare, and acute exacerbation of IP is a major cause of death in such cases...
December 8, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29225014/leber-s-hereditary-optic-neuropathy-caused-by-a-mutation-in-mitochondrial-trnathr-in-eight-chinese-pedigrees
#11
Juanjuan Zhang, Yanchun Ji, Xiaoling Liu, Jie Chen, Bibin Wang, Minglian Zhang, Min-Xin Guan
PURPOSE: The purpose of this study was to investigate the pathophysiology underlying Leber's hereditary optic neuropathy (LHON)-associated mitochondrial tRNA mutation. METHODS: Severn hundred ninety-seven Han Chinese subjects underwent clinical and genetic evaluation and analysis of mitochondrial DNA (mtDNA). The cybrid cell lines were constructed by transferring mitochondria from lymphoblastoid cell lines derived from a Chinese family into mtDNA-less (ρo) cells...
December 7, 2017: Mitochondrion
https://www.readbyqxmd.com/read/29224302/-clinical-and-radiological-features-of-adult-patients-with-different-antisynthetase-syndrome-based-on-serum-anti-aminoacyl-trna-synthetase-antibody-type
#12
S Li, H Huang, X Y Song, K Xu, C Y Wu, Q Wang, Z J Xu
Objective: To describe the clinical and radiological characteristics of antisynthetase syndrome associated interstitial lung disease in patients with different serum anti-aminoacyl-tRNA synthetase antibodies. Methods: We conducted a retrospective analysis of 5 adult patients with antisynthetase syndrome associated interstitial lung disease in Peking Union Medical College Hospital. Their clinical and chest radiological data were analyzed and relevant literatures were reviewed. Results: Among these 5 patients, there were 1 male and 4 females, aged from 32 y to 67 y, with a mean age of 53 y...
December 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/29223159/factors-beyond-enolase-2-and-mitochondrial-lysyl-trna-synthetase-precursor-are-required-for-trna-import-into-yeast-mitochondria
#13
M V Baleva, M Meyer, N Entelis, I Tarassov, P Kamenski, B Masquida
In yeast, the import of tRNALys with CUU anticodon (tRK1) relies on a complex mechanism where interaction with enolase 2 (Eno2p) dictates a deep conformational change of the tRNA. This event is believed to mask the tRNA from the cytosolic translational machinery to re-direct it towards the mitochondria. Once near the mitochondrial outer membrane, the precursor of the mitochondrial lysyl-tRNA synthetase (preMsk1p) takes over enolase to carry the tRNA within the mitochondrial matrix, where it is supposed to participate in translation following correct refolding...
November 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/29222331/a-hypertension-associated-mitochondrial-dna-mutation-introduces-an-m1g37-modification-into-trnamet-altering-its-structure-and-function
#14
Mi Zhou, Ling Xue, Yaru Chen, Haiying Li, Qiufen He, Bibin Wang, Feilong Meng, Meng Wang, Min-Xin Guan
Defective nucleotide modifications of mitochondrial tRNAs have been associated with several human diseases, but their pathophysiology remains poorly understood. In this report, we investigated the pathogenic molecular mechanism underlying a hypertension-associated 4435A>G mutation in mitochondrial tRNAMet The m.4435A>G mutation affected a highly conserved adenosine at position 37, 3' adjacent to the tRNA's anticodon, which is important for the fidelity of codon recognition and stabilization. We hypothesized that the m...
December 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29222070/regulation-of-trna-biogenesis-in-plants-and-its-link-to-plant-growth-and-response-to-pathogens
#15
REVIEW
Adriana Santos Soprano, Juliana Helena Costa Smetana, Celso Eduardo Benedetti
tRNA biology has fascinated scientists over the years. Besides their fundamental role in protein translation, new evidence indicates that tRNA-derived molecules also regulate gene expression and protein synthesis in all domains of life. In this review, we will highlight some of the recent findings linking tRNA transcription and modification with plant cell growth and response to pathogens. In fact, mutations in proteins directly involved in tRNA synthesis and modification most often lead to pleiotropic effects on plant growth and immunity...
December 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29222069/cooperativity-between-different-trna-modifications-and-their-modification-pathways
#16
REVIEW
Mikołaj Sokołowski, Roland Klassen, Alexander Bruch, Raffael Schaffrath, Sebastian Glatt
Ribonucleotide modifications perform a wide variety of roles in synthesis, turnover and functionality of tRNA molecules. The presence of particular chemical moieties can refine the internal interaction network within a tRNA molecule, influence its thermodynamic stability, contribute novel chemical properties and affect its decoding behavior during mRNA translation. As the lack of specific modifications in the anticodon stem and loop causes disrupted proteome homeostasis, diminished response to stress conditions, and the onset of human diseases, the underlying modification cascades have recently gained particular scientific and clinical interest...
December 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29221463/correction-to-recessive-vars2-mutation-underlies-a-novel-syndrome-with-epilepsy-mental-retardation-short-stature-growth-hormone-deficiency-and-hypogonadism
#17
Abdulaziz Alsemari, Banan Al-Younes, Ewa Goljan, Dyala Jaroudi, Faisal BinHumaid, Brian F Meyer, Stefan T Arold, Dorota Monies
After publication of the article [1], it has been brought to our attention that there is a nomenclature issue with this article. At the time of acceptance, the VARS2 mutation was considered equivalent to the VARS2 mutation. However, this has changed so that VARS now only refers to shorter mitochondrial sequence of valyl-tRNA synthesase containing 1093 amino acids. "Therefore, in the context of this article, every usage of "VARS2" should be replaced with "VARS" when referring to the causative variant".
December 8, 2017: Human Genomics
https://www.readbyqxmd.com/read/29221134/a-trna-fragment-trf5-glu-regulates-bcar3-expression-and-proliferation-in-ovarian-cancer-cells
#18
Kun Zhou, Kevin W Diebel, Jon Holy, Andrew Skildum, Evan Odean, Douglas A Hicks, Brent Schotl, Juan E Abrahante, Monique A Spillman, Lynne T Bemis
Ovarian cancer is a complex disease marked by tumor heterogeneity, which contributes to difficulties in diagnosis and treatment. New molecular targets and better molecular profiles defining subsets of patients are needed. tRNA fragments (tRFs) offer a recently identified group of noncoding RNAs that are often as abundant as microRNAs in cancer cells. Initially their presence in deep sequencing data sets was attributed to the breakdown of mature tRNAs, however, it is now clear that they are actively generated and function in multiple regulatory events...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29219730/a-comprehensive-profile-of-circulating-rnas-in-human-serum
#19
Sinan Uğur Umu, Hilde Langseth, Cecilie Bucher-Johannessen, Bastian Fromm, Andreas Keller, Eckart Meese, Marianne Lauritzen, Magnus Leithaug, Robert Lyle, Trine B Rounge
Non-coding RNA (ncRNA) molecules have fundamental roles in cells and many are also stable in body fluids as extracellular RNAs. In this study, we used RNA sequencing (RNA-seq) to investigate the profile of small non-coding RNA (sncRNA) in human serum. We analyzed 10 billion Illumina reads from 477 serum samples, included in the Norwegian population-based Janus Serum Bank (JSB). We found that the core serum RNA repertoire includes 258 micro RNAs (miRNA), 441 piwi-interacting RNAs (piRNA), 411 transfer RNAs (tRNA), 24 small nucleolar RNAs (snoRNA), 125 small nuclear RNAs (snRNA) and 123 miscellaneous RNAs (misc-RNA)...
December 8, 2017: RNA Biology
https://www.readbyqxmd.com/read/29216907/angiogenesis-and-vegf-expressing-cells-are-identified-predominantly-in-the-fascia-rather-than-in-the-muscle-during-the-early-phase-of-dermatomyositis
#20
Ken Yoshida, Haruyasu Ito, Kazuhiro Furuya, Taro Ukichi, Kentaro Noda, Daitaro Kurosaka
BACKGROUND: We previously demonstrated that fasciitis is a common lesion in dermatomyositis (DM) and that DM-associated fasciitis is detectable, as the result of the increased vascularity in the fascia, by power Doppler ultrasonography. We aimed to investigate whether angiogenesis and vascular endothelial growth factor (VEGF)-expressing cells in the fascia are histologically demonstrated during the early phase of DM, and whether inflammation is involved in angiogenesis and an increased number of VEGF-expressing cells...
December 8, 2017: Arthritis Research & Therapy
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