Abstract:
:Long noncoding RNAs (lncRNAs) play critical roles during tumorigenesis by functioning as scaffolds that regulate protein-protein, protein-DNA or protein-RNA interactions. Using a clinically guided genetic screening approach, we identified lncRNA in nonhomologous end joining (NHEJ) pathway 1 (LINP1), which is overexpressed in human triple-negative breast cancer. We found that LINP1 enhances repair of DNA double-strand breaks by serving as a scaffold linking Ku80 and DNA-PKcs, thereby coordinating the NHEJ pathway. Importantly, blocking LINP1, which is regulated by p53 and epidermal growth factor receptor (EGFR) signaling, increases the sensitivity of the tumor-cell response to radiotherapy in breast cancer.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Zhang Y,He Q,Hu Z,Feng Y,Fan L,Tang Z,Yuan J,Shan W,Li C,Hu X,Tanyi JL,Fan Y,Huang Q,Montone K,Dang CV,Zhang Ldoi
10.1038/nsmb.3211subject
Has Abstractpub_date
2016-06-01 00:00:00pages
522-30issue
6eissn
1545-9993issn
1545-9985pii
nsmb.3211journal_volume
23pub_type
杂志文章abstract::Thylakoid assembly 8 (THA8) is a pentatricopeptide repeat (PPR) RNA-binding protein required for the splicing of the transcript of ycf3, a gene involved in chloroplast thylakoid-membrane biogenesis. Here we report the identification of multiple THA8-binding sites in the ycf3 intron and present crystal structures of Br...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2710
更新日期:2013-12-01 00:00:00
abstract::In this article, the Ponceau staining presented in Fig. 1b (right, bottom) does not follow best practices for figure preparation since itinadvertently included duplications from the Ponceau staining presented in Supplementary Fig. 1b (for which the same preparation ofnucleosomes from HeLa cells had been used). A new F...
journal_title:Nature structural & molecular biology
pub_type: 已发布勘误
doi:10.1038/s41594-018-0090-0
更新日期:2018-08-01 00:00:00
abstract::The discovery of the three eukaryotic nuclear RNA polymerases paved the way for serious biochemical investigations of eukaryotic transcription and the identification of eukaryotic transcription factors. Here we describe this adventure from our vantage point, with a focus on the hunt for factors that regulate elongatio...
journal_title:Nature structural & molecular biology
pub_type: 历史文章,杂志文章,评审
doi:10.1038/s41594-019-0283-1
更新日期:2019-09-01 00:00:00
abstract::Histone H3 Lys4 (H3K4) is methylated by yeast Set1-COMPASS and its mammalian homolog, the MLL complex. Human JARID1d can demethylate trimethyl-H3K4 (H3K4me3). We identified Drosophila melanogaster little imaginal discs (Lid) as the JARID1d homolog. We report that Lid knockdown using RNA interference results in a speci...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb1217
更新日期:2007-04-01 00:00:00
abstract::Although tertiary folding of whole protein domains is prohibited by the cramped dimensions of the ribosomal tunnel, dynamic tertiary interactions may permit folding of small elementary units within the tunnel. To probe this possibility, we used a beta-hairpin and an alpha-helical hairpin from the cytosolic N terminus ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1571
更新日期:2009-04-01 00:00:00
abstract::Microtubules are regulated by post-translational modifications of tubulin. The ligation and cleavage of the carboxy-terminal tyrosine of α-tubulin impact microtubule functions during mitosis, cardiomyocyte contraction and neuronal processes. Tubulin tyrosination and detyrosination are mediated by tubulin tyrosine liga...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-019-0242-x
更新日期:2019-07-01 00:00:00
abstract::Chaperones, a group of proteins that assist the folding of other proteins, seem to work in a coordinated manner. Two major chaperone families are heat-shock protein families Hsp60 and Hsp70. Here we show for the first time the formation of a stable complex between chaperonin-containing TCP-1 (CCT) and Hsc70, two eukar...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1464
更新日期:2008-08-01 00:00:00
abstract::Inconsistent with prevailing models for nonsense-mediated mRNA decay (NMD) in mammals, the mRNA levels of immunoglobulin-mu (Ig-mu) genes with premature termination codons (PTCs) in the penultimate exon are still reduced by NMD when the intron furthest downstream is deleted. As in yeast, this exon junction complex-ind...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb1081
更新日期:2006-05-01 00:00:00
abstract::Aggregation of proteins containing polyglutamine (polyQ) expansions characterizes many neurodegenerative disorders, including Huntington's disease. Molecular chaperones modulate the aggregation and toxicity of the huntingtin (Htt) protein by an ill-defined mechanism. Here we determine how the chaperonin TRiC suppresse...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1700
更新日期:2009-12-01 00:00:00
abstract::The interaction of autotaxin with its substrates leads to the production of lysophosphatidic acids (LPA), bioactive lipids with an emerging prominent role in inflammation and cancer. Two papers in this issue tell the previously unknown story of autotaxin, from substrate discrimination to highly efficient local deliver...
journal_title:Nature structural & molecular biology
pub_type: 评论,杂志文章
doi:10.1038/nsmb0211-117
更新日期:2011-02-01 00:00:00
abstract::Glucokinase (GK) is a glucose-phosphorylating enzyme that regulates insulin release and hepatic metabolism, and its loss of function is implicated in diabetes pathogenesis. GK activators (GKAs) are attractive therapeutics in diabetes; however, clinical data indicate that their benefits can be offset by hypoglycemia, o...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2717
更新日期:2014-01-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature structural & molecular biology
pub_type: 已发布勘误
doi:10.1038/s41594-020-00531-z
更新日期:2020-12-01 00:00:00
abstract::The exosome is an RNA-decay complex that constantly monitors transcription and contributes to post-transcriptional turnover of faulty mRNAs. Yet how nuclear RNA surveillance by the exosome is coordinated with transcription is still unknown. Here we show that the RNA exosome of Schizosaccharomyces pombe can target the ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2893
更新日期:2014-10-01 00:00:00
abstract::Proteins regulate gene expression by controlling mRNA biogenesis, localization, translation and decay. Identifying the composition, diversity and function of mRNA-protein complexes (mRNPs) is essential to understanding these processes. In a global survey of Saccharomyces cerevisiae mRNA-binding proteins, we identified...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2468
更新日期:2013-01-01 00:00:00
abstract::In bacteria, incorporation of selenocysteine, the 21(st) amino acid, into proteins requires elongation factor SelB, which has the unusual property of binding to both transfer RNA (tRNA) and mRNA. SelB binds to an mRNA hairpin formed by the selenocysteine insertion sequence (SECIS) with extremely high specificity, the ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb890
更新日期:2005-02-01 00:00:00
abstract::Messenger RNAs produced by splicing are translated more efficiently than those produced from similar intronless precursor mRNAs (pre-mRNAs). The exon-junction complex (EJC) probably mediates this enhancement; however, the specific link between the EJC and the translation machinery has not been identified. The EJC prot...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb1321
更新日期:2007-12-01 00:00:00
abstract::Heat-shock transcription factor (HSF) family members function in stress protection and in human diseases including proteopathies, neurodegeneration and cancer. The mechanisms that drive distinct post-translational modifications, cofactor recruitment and target-gene activation for specific HSF paralogs are unknown. We ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.3150
更新日期:2016-02-01 00:00:00
abstract::Despite growing appreciation of the importance of long noncoding RNAs (lncRNAs) in normal physiology and disease, our knowledge of cancer-related lncRNAs remains limited. By repurposing microarray probes, we constructed expression profiles of 10,207 lncRNA genes in approximately 1,300 tumors over four different cancer...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2591
更新日期:2013-07-01 00:00:00
abstract::We investigated co-transcriptional recruitment of pre-mRNA processing factors to human genes. Capping factors associate with paused RNA polymerase II (pol II) at the 5' ends of quiescent genes. They also track throughout actively transcribed genes and accumulate with paused polymerase in the 3' flanking region. The 3'...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb1352
更新日期:2008-01-01 00:00:00
abstract::The Ca(2+) sensor synaptotagmin-1 is thought to trigger membrane fusion by binding to acidic membrane lipids and SNARE proteins. Previous work has shown that binding is mediated by electrostatic interactions that are sensitive to the ionic environment. However, the influence of divalent or polyvalent ions, at physiolo...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.3097
更新日期:2015-10-01 00:00:00
abstract::A fundamental question is how enzymes can accelerate chemical reactions. Catalysis is not only defined by actual chemical steps, but also by enzyme structure and dynamics. To investigate the role of protein dynamics in enzymatic turnover, we measured residue-specific protein dynamics in hyperthermophilic and mesophili...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb821
更新日期:2004-10-01 00:00:00
abstract::The N-end rule pathway is a regulated proteolytic system that targets proteins containing destabilizing N-terminal residues (N-degrons) for ubiquitination and proteasomal degradation in eukaryotes. The N-degrons of type 1 substrates contain an N-terminal basic residue that is recognized by the UBR box domain of the E3...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1907
更新日期:2010-10-01 00:00:00
abstract::The tumor suppressor p53 has been proposed to bind target promoters upon genotoxic stress. However, recent evidence shows that p53 occupies some target promoters without such stress, suggesting that a negative regulator might render p53 transcriptionally inactive on these promoters. Here we show that calcineurin bindi...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1657
更新日期:2009-09-01 00:00:00
abstract::Bacterial transcription is controlled by sigma factors, the RNA polymerase subunits that act as initiation factors. Although a single housekeeping sigma factor enables transcription from thousands of promoters, environmentally induced sigma factors redirect gene expression toward small regulons to carry out focused re...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2777
更新日期:2014-03-01 00:00:00
abstract::Domain 5 (D5) is the central core of group II intron ribozymes. Many base and backbone substituents of this highly conserved hairpin participate in catalysis and are crucial for binding to other intron domains. We report the solution structures of the 34-nucleotide D5 hairpin from the group II intron ai5 gamma in the ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb717
更新日期:2004-02-01 00:00:00
abstract::In mammalian cells, nonsense-mediated messenger RNA decay (NMD) targets newly synthesized nonsense-containing mRNA bound by the cap-binding-protein heterodimer CBP80-CBP20 and at least one exon-junction complex (EJC). An EJC includes the NMD factors Upf3 or Upf3X and Upf2, and Upf2 recruits Upf1. Once this pioneer tra...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb995
更新日期:2005-10-01 00:00:00
abstract::Histones have two structurally and functionally distinct domains: globular domains forming the nucleosomal core around which DNA is wrapped and unstructured tails protruding from the nucleosomal core. Whereas post-translational modifications (PTMs) in histone tails are well studied, much less is currently known about ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2581
更新日期:2013-06-01 00:00:00
abstract::The eukaryotic DNA replication machinery must traverse every nucleosome in the genome during S phase. As nucleosomes are generally inhibitory to DNA-dependent processes, chromatin structure must undergo extensive reorganization to facilitate DNA synthesis. However, the identity of chromatin-remodeling factors involved...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1419
更新日期:2008-05-01 00:00:00
abstract::Although t-loops protect telomeres, they are at risk of cleavage by Holliday junction (HJ) resolvases if branch migration converts the three-way t-loop junction into four-way HJs. T-loop cleavage is repressed by the TRF2 basic domain, which binds three- and four-way junctions and protects HJs in vitro. By replacing th...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.3451
更新日期:2017-09-01 00:00:00
abstract::The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-ric...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-018-0064-2
更新日期:2018-06-01 00:00:00