Abstract:
:The tissue specificity of mitochondrial tRNA mutations remains largely elusive. In this study, we demonstrated the deleterious effects of tRNAThr 15927G>A mutation that contributed to pathogenesis of coronary artery disease. The m.15927G>A mutation abolished the highly conserved base-pairing (28C-42G) of anticodon stem of tRNAThr. Using molecular dynamics simulations, we showed that the m.15927G>A mutation caused unstable tRNAThr structure, supported by decreased melting temperature and slower electrophoretic mobility of mutated tRNA. Using cybrids constructed by transferring mitochondria from a Chinese family carrying the m.15927G>A mutation and a control into mitochondrial DNA (mtDNA)-less human umbilical vein endothelial cells, we demonstrated that the m.15927G>A mutation caused significantly decreased efficiency in aminoacylation and steady-state levels of tRNAThr. The aberrant tRNAThr metabolism yielded variable decreases in mtDNA-encoded polypeptides, respiratory deficiency, diminished membrane potential and increased the production of reactive oxygen species. The m.15927G>A mutation promoted the apoptosis, evidenced by elevated release of cytochrome c into cytosol and increased levels of apoptosis-activated proteins: caspases 3, 7, 9 and PARP. Moreover, the lower wound healing cells and perturbed tube formation were observed in mutant cybrids, indicating altered angiogenesis. Our findings provide new insights into the pathophysiology of coronary artery disease, which is manifested by tRNAThr mutation-induced alterations.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Jia Z,Zhang Y,Li Q,Ye Z,Liu Y,Fu C,Cang X,Wang M,Guan MXdoi
10.1093/nar/gky1241subject
Has Abstractpub_date
2019-02-28 00:00:00pages
2056-2074issue
4eissn
0305-1048issn
1362-4962pii
5239030journal_volume
47pub_type
杂志文章abstract::The RNA 3D Structure-to-Multiple Sequence Alignment Server (R3D-2-MSA) is a new web service that seamlessly links RNA three-dimensional (3D) structures to high-quality RNA multiple sequence alignments (MSAs) from diverse biological sources. In this first release, R3D-2-MSA provides manual and programmatic access to cu...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv543
更新日期:2015-07-01 00:00:00
abstract::The identification of genes with specific patterns of change (e.g. down-regulated and methylated) as phenotype drivers or samples with similar profiles for a given gene set as drivers of clinical outcome, requires the integration of several genomic data types for which an 'integrate by intersection' (IBI) approach is ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv1503
更新日期:2016-04-20 00:00:00
abstract::The PROSITE pattern Zinc_Finger_C2H2 was extended to permit the detection of all C2H2 zinc fingers and their parent proteins in the recently completed sequence of the yeast genome. Additionally, a new computer program was written that extracts other zinc binding motifs (non C2H2 'fingers'), overlapping with the classi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/25.12.2464
更新日期:1997-06-15 00:00:00
abstract::The structural simplicity and ability to capture serial correlations make Markov models a popular modeling choice in several genomic analyses, such as identification of motifs, genes and regulatory elements. A critical, yet relatively unexplored, issue is the determination of the order of the Markov model. Most biolog...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks1285
更新日期:2013-02-01 00:00:00
abstract::The rol-6 gene is trans-spliced to the 22 nt leader, SL1, 173 nt downstream of the transcription start. We have analyzed splicing in transformants carrying extrachromosomal arrays of rol-6 with mutations in the trans-splice acceptor site. This site is a close match to the consensus, UUUCAG, that is highly conserved in...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.4.913
更新日期:1993-02-25 00:00:00
abstract::Bursts of free radicals produced by ionization of water in close vicinity to DNA can produce clusters of opposed DNA lesions and these are termed multiply damaged sites (MDS). How MDS are processed by the Escherichia coli DNA glycosylases, endonuclease (endo) III and endo VIII, which recognize oxidized pyrimidines, is...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.4.932
更新日期:1998-02-15 00:00:00
abstract::We have previously reported that transcription from a distal promoter (promoter B) of the estrogen receptor alpha (ERalpha) gene is responsible for the increased expression of ERalpha in human breast carcinomas. This paper first characterized the promoter B region in terms of transient transfection experiments with lu...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/27.3.903
更新日期:1999-02-01 00:00:00
abstract::We have used computer assisted dot matrix and oligonucleotide frequency analyses to identify highly recurring sequence elements of 7-11 base pairs in eukaryotic genes and viral DNAs. Such elements are found much more frequently than expected, often with an average spacing of a few hundred base pairs. Furthermore, the ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/15.4.1835
更新日期:1987-02-25 00:00:00
abstract::Inadequate cellular compartmentalisation of plasmid DNA and antisense oligodeoxynucleotides (ODNs) is generally considered as a major limitation in their use. In this study, an approach combining in situ visual-isation of rhodamine-labelled ODNs and affinity modification of proteins by radiolabelled-alkylating ODN der...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/27.11.2315
更新日期:1999-06-01 00:00:00
abstract::A cDNA clone named 1A11 was isolated in a screen for genes that are activated by both mesoderm inducing factors FGF and activin in animal explants of Xenopus laevis embryos. In undisturbed embryos, 1A11 is expressed during the gastrula stage in the entire marginal zone where mesoderm originates, and later in the somit...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.10.2375
更新日期:1993-05-25 00:00:00
abstract::To elucidate the response to oxidative stress in eukaryotic cells, the effect of an oxidized nucleotide, 8-oxo-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP), generated from dGTP with an active oxygen, on DNA synthesis was studied using a cell-free DNA replication system derived from Xenopus egg lysates with a single-...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/30.2.569
更新日期:2002-01-15 00:00:00
abstract::Many mutations occur as a result of DNA synthesis past the site of DNA damage by DNA damage bypass polymerases. The frequency and types of mutations not only depend on the nature of the damage, but also on the sequence context, as revealed from analysis of mutation spectra of DNA exposed to mutagens. Herein we report ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn595
更新日期:2008-10-01 00:00:00
abstract::We present web servers for analysis of non-coding RNA sequences on the basis of their secondary structures. Software tools for structural multiple sequence alignments, structural pairwise sequence alignments and structural motif findings are available from the integrated web server and the individual stand-alone web s...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn222
更新日期:2008-07-01 00:00:00
abstract::Chromosome stability is primarily determined by telomere length. TRF1 is the core subunit of shelterin that plays a critical role in telomere organization and replication. However, the dynamics of TRF1 in scenarios of telomere-processing activities remain elusive. Using single-molecule magnetic tweezers, we here inves...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa1222
更新日期:2021-01-25 00:00:00
abstract::We developed a sensitive 32P-postlabeling method for the detection of bifunctional intrastrand crosslinks d(Pt-GpG) and d(Pt-ApG) in DNA in vitro and in vivo. After enzymatic digestion of DNA the positively charged platinum adducts were purified from unplatinated products, using strong cation exchange chromatography. ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/23.8.1300
更新日期:1995-04-25 00:00:00
abstract::Fundamental aspects of the biochemistry of Type III restriction endonucleases remain unresolved despite being characterized by numerous research groups in the past decades. One such feature is the subunit stoichiometry of these hetero-oligomeric enzyme complexes, which has important implications for the reaction mecha...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gku122
更新日期:2014-04-01 00:00:00
abstract::Fifteen years elapsed between the discovery of the double helix (1953) and the first DNA sequencing (1968). Modern DNA sequencing began in 1977, with development of the chemical method of Maxam and Gilbert and the dideoxy method of Sanger, Nicklen and Coulson, and with the first complete DNA sequence (phage X174), whi...
journal_title:Nucleic acids research
pub_type: 历史文章,杂志文章
doi:10.1093/nar/gkm688
更新日期:2007-01-01 00:00:00
abstract::The laboratory mouse is the premier animal model for studying human biology because all life stages can be accessed experimentally, a completely sequenced reference genome is publicly available and there exists a myriad of genomic tools for comparative and experimental research. In the current era of genome scale, dat...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks1115
更新日期:2013-01-01 00:00:00
abstract::A flow-injection (FI) device is combined, through the use of a low-volume (4 microl) flow cell, with an ultrasensitive surface plasmon resonance (SPR) spectrometer equipped with a bi-cell photodiode detector. The application of this novel FI-SPR device for sequence-specific ultratrace analysis of oligodeoxynucleotides...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gnf072
更新日期:2002-07-15 00:00:00
abstract::Differences between species have been suggested to largely reside in the network of connections among the genes. Nevertheless, the rate at which these connections evolve has not been properly quantified. Here, we measure the extent to which co-regulation between pairs of genes is conserved over large phylogenetic dist...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh815
更新日期:2004-09-07 00:00:00
abstract::Mixed-lineage leukemia (MLL) maintains the expression of cellular memory genes during development, while leukemic MLL fusion proteins aberrantly maintain expression of hematopoietic stem cell program genes such as HOXA9 to cause leukemia. However, the molecular mechanism of gene activation is unclear. Here we show tha...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt1394
更新日期:2014-04-01 00:00:00
abstract::Transcription start and termination sites were mapped in the E. coli replication origin, oriC. Outward transcription from within oriC (promoters Pori-r and Pori-l) was found to start in vivo at position 178 for Pori-l and at positions 294 and 304 for Pori-r, respectively. These transcripts were terminated after 100-15...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/15.6.2479
更新日期:1987-03-25 00:00:00
abstract::G-quadruplexes are dynamic structures folded in G-rich single-stranded DNA regions. These structures have been recognized as a potential nucleic acid based mechanism for regulating multiple cellular processes such as replication, transcription and genomic maintenance. So far, their transcriptional role in vivo during ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw011
更新日期:2016-05-19 00:00:00
abstract::Purified UvrA, UvrB, UvrC, UvrD, PolA and Lig proteins from Escherichia coli have been used to assess the effect of nucleotide excision repair on the conformation of native negatively supercoiled plasmid DNA in an in vitro test system. The analysis of labeled reaction products on specific gel systems suggests that the...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/17.24.10337
更新日期:1989-12-25 00:00:00
abstract::Dlx homeobox genes are first expressed in embryonic retina at E11.5. The Dlx1/Dlx2 null retina has a reduced ganglion cell layer (GCL), with loss of late-born differentiated retinal ganglion cells (RGCs) due to increased apoptosis. TrkB signaling is proposed to regulate the dynamics of RGC apoptosis throughout develop...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm1099
更新日期:2008-02-01 00:00:00
abstract::We analysed the basic mechanisms of signal transmission in DNA and the origins of the allostery exhibited by systems such as the ternary complex BAMHI-DNA-GRDBD. We found that perturbation information generated by a primary protein binding event travels as a wave to distant regions of DNA following a hopping mechanism...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky549
更新日期:2018-09-06 00:00:00
abstract::Synonymous codon usage significantly impacts translational and transcriptional efficiency, gene expression, the secondary structure of both mRNA and proteins, and has been implicated in various diseases. However, population-specific differences in codon usage biases remain largely unexplored. Here, we present a web se...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa863
更新日期:2020-11-04 00:00:00
abstract::We have developed a highly sensitive method for DNA analysis on 3D gel element microarrays, a technique we call multiplex microarray-enhanced PCR (MME-PCR). Two amplification strategies are carried out simultaneously in the reaction chamber: on or within gel elements, and in bulk solution over the gel element array. M...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gnh184
更新日期:2005-01-20 00:00:00
abstract::Protein-protein interactions regulate many essential enzymatic processes in the cell. Somatic mutations outside of an enzyme active site can therefore impact cellular function by disruption of critical protein-protein interactions. In our investigation of the cellular impact of the T304I cancer mutation of DNA Polymer...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz293
更新日期:2019-07-09 00:00:00
abstract::DNA target recognizing domains of different multispecific DNA-cytosine-methyltransferases can be rearranged through engineering of the corresponding genes to generate enzymes with novel combinations of target recognition. ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/16.14.6649
更新日期:1988-07-25 00:00:00