Abstract:
:Mutations in human mitochondrial DNA are often associated with incurable human neuromuscular diseases. Among these mutations, an important number have been identified in tRNA genes, including 29 in the gene MT-TL1 coding for the tRNA(Leu(UUR)). The m.3243A>G mutation was described as the major cause of the MELAS syndrome (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes). This mutation was reported to reduce tRNA(Leu(UUR)) aminoacylation and modification of its anti-codon wobble position, which results in a defective mitochondrial protein synthesis and reduced activities of respiratory chain complexes. In the present study, we have tested whether the mitochondrial targeting of recombinant tRNAs bearing the identity elements for human mitochondrial leucyl-tRNA synthetase can rescue the phenotype caused by MELAS mutation in human transmitochondrial cybrid cells. We demonstrate that nuclear expression and mitochondrial targeting of specifically designed transgenic tRNAs results in an improvement of mitochondrial translation, increased levels of mitochondrial DNA-encoded respiratory complexes subunits, and significant rescue of respiration. These findings prove the possibility to direct tRNAs with changed aminoacylation specificities into mitochondria, thus extending the potential therapeutic strategy of allotopic expression to address mitochondrial disorders.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Karicheva OZ,Kolesnikova OA,Schirtz T,Vysokikh MY,Mager-Heckel AM,Lombès A,Boucheham A,Krasheninnikov IA,Martin RP,Entelis N,Tarassov Idoi
10.1093/nar/gkr546subject
Has Abstractpub_date
2011-10-01 00:00:00pages
8173-86issue
18eissn
0305-1048issn
1362-4962pii
gkr546journal_volume
39pub_type
杂志文章abstract::UMSBP is a CCHC-type zinc finger protein, which functions during replication initiation of kinetoplast DNA minicircles and the segregation of kinetoplast DNA networks. Interactions of UMSBP with origin sequences, as well as the protein oligomerization, are affected by its redox state. Reduction yields UMSBP monomers a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn927
更新日期:2009-01-01 00:00:00
abstract::Prion proteins (PrPs) cause prion diseases, such as bovine spongiform encephalopathy. The conversion of a normal cellular form (PrP(C)) of PrP into an abnormal form (PrP(Sc)) is thought to be associated with the pathogenesis. An RNA aptamer that tightly binds to and stabilizes PrP(C) is expected to block this conversi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks1132
更新日期:2013-01-01 00:00:00
abstract::Most proteins from higher organisms are known to be multi-domain proteins and contain substantial numbers of intrinsically disordered (ID) regions. To analyse such protein sequences, those from human for instance, we developed a special protein-structure-prediction pipeline and accumulated the products in the Structur...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq1057
更新日期:2011-01-01 00:00:00
abstract::RNase D was recently reported as a new enzymatic activity associated with HIV-1 reverse transcriptase (RT), cleaving RNA at two positions within the double-stranded region of the tRNA primer-viral RNA template complex (Ben-Artzi et al., Proc. Natl. Acad. Sci. USA 89 (1992) 927-931). This would make RNase D a fourth di...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/20.21.5819
更新日期:1992-11-11 00:00:00
abstract::Arylsulfatase, produced by Chlamydomonas reinhardtii during sulfur-limited growth, is secreted into the periplasmic space and is readily assayed using a chromogenic substrate. To assess the usefulness of the gene encoding arylsulfatase (ars) as a reporter gene in C. reinhardtii, we have fused the promoter region of th...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/20.12.2959
更新日期:1992-06-25 00:00:00
abstract::Available evidence suggests that Mg2+ ions are involved in reactions catalyzed by hammerhead ribozymes. However, the activity in the presence of exclusively monovalent ions led us to question whether divalent metal ions really function as catalysts when they are present. We investigated ribozyme activity in the presen...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh753
更新日期:2004-08-09 00:00:00
abstract::The effect of amino groups attached at positions 2 and 8 of the hypoxanthine moiety in the structure, reactivity and stability of DNA duplexes and triplexes is studied by means of quantum mechanical calculations, as well as extended molecular dynamics (MD) and thermodynamic integration (MD/TI) simulations. Theoretical...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.12.2522
更新日期:2001-06-15 00:00:00
abstract::The synthesis of cyclic di-, tri-, tetra-, penta- and hexa-thymidylic acids (16; n = 2, 3, 4, 5 and 6) and the cyclic hexadeoxyribonucleotide [d(CpCpTpApGpGp)], via the "filtration" approach, is reported. Some of the physical properties of the cyclic oligonucleotides are discussed, and their susceptibility to digestio...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/17.20.8221
更新日期:1989-10-25 00:00:00
abstract::Planarian flatworms are in the midst of a renaissance as a model system for regeneration and stem cells. Besides two well-studied model species, hundreds of species exist worldwide that present a fascinating diversity of regenerative abilities, tissue turnover rates, reproductive strategies and other life history trai...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv1148
更新日期:2016-01-04 00:00:00
abstract::Insertion of the four major nucleotides at the 5'-side of the anticodon triplet of E. coli tRNAMetf was performed by joining of the half molecules obtained by limited digestion with RNase A and the chemically synthesized tetranucleotide pN-C-A-U using RNA ligase. Insertion of U-U at the 5'-side or A and A-A at the 3'-...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/13.10.3685
更新日期:1985-05-24 00:00:00
abstract::The Sleeping Beauty (SB) transposon is a promising gene transfer vector that integrates nonspecifically into host cell genomes. Herein, we attempt to direct transposon integration into predetermined DNA sites by coupling a site-specific DNA-binding domain (DBD) to the SB transposase. We engineered fusion proteins comp...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm089
更新日期:2007-01-01 00:00:00
abstract::Rapid characterization of unknown biological samples is under the focus of many current studies. Here we report a method for screening of biological samples by optical mapping of their DNA. We use a novel, one-step chemo-enzymatic reaction to covalently bind fluorophores to DNA at the four-base recognition sites of a ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv563
更新日期:2015-10-15 00:00:00
abstract::It has recently been demonstrated that nucleobase-density profiles of typical mRNA coding sequences exhibit a complementary relationship with nucleobase-interaction propensity profiles of their cognate protein sequences. This finding supports the idea that the genetic code developed in response to direct binding inter...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv166
更新日期:2015-03-31 00:00:00
abstract::Superhelical PM2 DNA can be photochemically modified by u.v. irradiation. The variation of S20,w with dose shows the following characteristics. There is a linear increase from 28 to 31s produced by a low dose of u.v. irradiation (4,000 ergs/mm2). A plateau in S20,w occurs between 4,000 and 10,000 ergs/mm2. The S20,w t...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/4.5.1243
更新日期:1977-01-01 00:00:00
abstract::A better understanding of transcriptional and post-transcriptional regulation of gene expression in bacteria relies on studying their transcriptome. RNA sequencing methods are used not only to assess RNA abundance but also the exact boundaries of primary and processed transcripts. Here, we developed a method, called i...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw1316
更新日期:2017-03-17 00:00:00
abstract::To facilitate transcript mapping and to investigate alterations in genomic structure and gene expression in a defined genomic target, we developed a novel microarray-based method to detect transcriptional activity of the human chromosome 4q22-24 region. Loss of heterozygosity of human 4q22-24 is frequently observed in...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gnh025
更新日期:2004-02-11 00:00:00
abstract::Glucocorticoid (GC) signaling synchronizes the circadian rhythm of individual peripheral cells and induces the expression of circadian genes, including Period1 (Per1) and Period2 (Per2). However, no GC response element (GRE) has been reported in the Per2 promoter region. Here we report the molecular mechanisms of Per2...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt307
更新日期:2013-07-01 00:00:00
abstract::We have developed a new method for analysis of complex genetic systems by a combination of the Amplification Refractory Mutation System (ARMS) and Single-Strand Conformation Polymorphism (SSCP) analysis: ARMS-SSCP. Thus, a complex allelic series is subdivided into a number of groups by ARMS followed by the identificat...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/20.5.1005
更新日期:1992-03-11 00:00:00
abstract::Protein-induced DNA bending is of importance in the formation of complex nucleoprotein assemblies such as those involved in the initiation of DNA replication or transcription initiation. We have compared the DNA bending characteristics of the Escherichia coli cyclic AMP receptor protein (CRP or CAP), an archetypal DNA...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/20.13.3391
更新日期:1992-07-11 00:00:00
abstract::Retinoic acid-inducible gene I (RIG-I) is a pattern recognition receptor expressed in metazoan cells that is responsible for eliciting the production of type I interferons and pro-inflammatory cytokines upon detection of intracellular, non-self RNA. Structural studies of RIG-I have identified a novel Pincer domain com...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gku817
更新日期:2014-10-01 00:00:00
abstract::Galahad (https://galahad.esat.kuleuven.be) is a web-based application for analysis of drug effects. It provides an intuitive interface to be used by anybody interested in leveraging microarray data to gain insights into the pharmacological effects of a drug, mainly identification of candidate targets, elucidation of m...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv436
更新日期:2015-07-01 00:00:00
abstract::Major efforts are underway to elucidate the spatial distribution of ribosomal RNAs (rRNAs) in the ribosome. An especially informative approach is the identification of likely base-base tertiary interactions within the RNA by phylogenetic comparison. Herein evidence is presented for three heretofore unrecognized candid...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/17.6.2215
更新日期:1989-03-25 00:00:00
abstract::The replication origin (oriC) of the Escherichia coli chromosome has been cloned and the region essential for chromosomal replication has been delimited to 245 base pairs. In previous studies the ability of recombinants between oriC and ColE1-type vectors, to transform E. coli polA- strains was used to determine which...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/11.22.8007
更新日期:1983-11-25 00:00:00
abstract::We investigated how Escherichia coli ClpXP targets the helicase-nuclease (HsdR) subunit of the bacterial Type I restriction-modification enzyme EcoKI during restriction alleviation (RA). RA is a temporary reduction in endonuclease activity that occurs when Type I enzymes bind unmodified recognition sites on the host g...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gku851
更新日期:2014-10-29 00:00:00
abstract::Annotation of herpesvirus genomes has traditionally been undertaken through the detection of open reading frames and other genomic motifs, supplemented with sequencing of individual cDNAs. Second generation sequencing and high-density microarray studies have revealed vastly greater herpesvirus transcriptome complexity...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw629
更新日期:2016-10-14 00:00:00
abstract::Transcription and translation are coupled in bacteria, meaning that translation takes place co-transcriptionally. During transcription-translation, both machineries mutually affect each others' functions, which is important for regulation of gene expression. Analysis of interactions between RNA polymerase (RNAP) and t...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr1262
更新日期:2012-03-01 00:00:00
abstract::IGF2 mRNA-binding protein 1 (IMP1) is a key regulator of messenger RNA (mRNA) metabolism and transport in organismal development and, in cancer, its mis-regulation is an important component of tumour metastasis. IMP1 function relies on the recognition of a diverse set of mRNA targets that is mediated by the combinator...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz136
更新日期:2019-05-07 00:00:00
abstract::Mono- and polyclonal antibodies directed against different domains of the potato leafroll luteovirus (PLRV) P1 (ORF1) protein were applied to the analysis of P1 expression during PLRV replication in planta. Western analyses detected P1 and a protein of approximately 25 kDa (P1-C25) that accumulated to readily detectab...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/27.2.421
更新日期:1999-01-15 00:00:00
abstract::DNA double-strand breaks (DSBs) and their repair can cause extensive epigenetic changes. As a result, DSBs have been proposed to promote transcriptional and, ultimately, physiological dysfunction via both cell-intrinsic and cell-non-autonomous pathways. Studying the consequences of DSBs in higher organisms has, howeve...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv1482
更新日期:2016-04-20 00:00:00
abstract::Double-strand breaks (DSBs) are dangerous chromosomal lesions that must be efficiently repaired in order to avoid loss of genetic information or cell death. In all organisms studied to date, two different mechanisms are used to repair DSBs: homologous recombination (HR) and non-homologous end joining (NHEJ). Previous ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm521
更新日期:2007-01-01 00:00:00