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 types. Through integrative analysis of the lncRNA expression profiles with clinical outcome and somatic copy-number alterations, we identified lncRNAs that are associated with cancer subtypes and clinical prognosis and predicted those that are potential drivers of cancer progression. We validated our predictions by experimentally confirming prostate cancer cell growth dependence on two newly identified lncRNAs. Our analysis provides a resource of clinically relevant lncRNAs for the development of lncRNA biomarkers and the identification of lncRNA therapeutic targets. It also demonstrates the power of integrating publically available genomic data sets and clinical information for discovering disease-associated lncRNAs.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Du Z,Fei T,Verhaak RG,Su Z,Zhang Y,Brown M,Chen Y,Liu XSdoi
10.1038/nsmb.2591subject
Has Abstractpub_date
2013-07-01 00:00:00pages
908-13issue
7eissn
1545-9993issn
1545-9985pii
nsmb.2591journal_volume
20pub_type
杂志文章abstract：:Hsp70s use ATP hydrolysis to disrupt protein-protein associations and to move macromolecules. One example is the Hsc70- mediated disassembly of the clathrin coats that form on vesicles during endocytosis. Here, we exploited the exceptional features of these coats to test three models-Brownian ratchet, power-stroke and...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.3272
更新日期：2016-09-01 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：:Immunoglobulin G4 antibodies exhibit unusual properties with important biological consequences. We report the structure of the human full-length IgG4 S228P anti-PD1 antibody pembrolizumab, solved to 2.3-Å resolution. Pembrolizumab is a compact molecule, consistent with the presence of a short hinge region. The Fc doma...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.3129
更新日期：2015-12-01 00:00:00
abstract：:Coupling between transcription and RNA processing is a key gene regulatory mechanism. Here we use chromatin immunoprecipitation to detect transcription-dependent accumulation of the precursor mRNA (pre-mRNA) splicing factors hnRNP A1, U2AF65 and U1 and U5 snRNPs on the intron-containing human FOS gene. These factors w...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1135
更新日期：2006-09-01 00:00:00
abstract：:Aquaporin (AQP) folding in the endoplasmic reticulum is characterized by two distinct pathways of membrane insertion that arise from divergent residues within the second transmembrane segment. We now show that in AQP1 these residues (Asn49 and Lys51) interact with Asp185 at the C terminus of TM5 to form a polar, quate...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1275
更新日期：2007-08-01 00:00:00
abstract：:Ribosomes translating secretory and membrane proteins are targeted to the endoplasmic reticulum membrane and attach to the protein-conducting channel and ribosome-associated membrane proteins (RAMPs). Recently, a new RAMP, ERj1p, has been identified that recruits BiP to ribosomes and regulates translational activity. ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb998
更新日期：2005-11-01 00:00:00
abstract：:Bacterial tRNA adenosine deaminases (TadAs) catalyze the hydrolytic deamination of adenosine to inosine at the wobble position of tRNA(Arg2), a process that enables this single tRNA to recognize three different arginine codons in mRNA. In addition, inosine is also introduced at the wobble position of multiple eukaryot...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1047
更新日期：2006-02-01 00:00:00
abstract：:We developed a 'computational second-site suppressor' strategy to redesign specificity at a protein-protein interface and applied it to create new specifically interacting DNase-inhibitor protein pairs. We demonstrate that the designed switch in specificity holds in in vitro binding and functional assays. We also show...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb749
更新日期：2004-04-01 00:00:00
abstract：:Neuronal communication is mediated by Ca(2+)-triggered fusion of transmitter-filled synaptic vesicles with the presynaptic plasma membrane. Synaptotagmin I functions as a Ca(2+) sensor that regulates exocytosis, whereas soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) proteins in th...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1463
更新日期：2008-08-01 00:00:00
abstract：:The WD40-repeat protein WDR5 is a conserved subunit of Trithorax (TRX) histone methyltransferase complexes. WDR5 has been reported to selectively bind dimethylated Lys4 (K4me2) in histone H3 to promote K4 trimethylation by TRX. To elucidate the basis of this binding specificity, we have determined the crystal structur...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1116
更新日期：2006-08-01 00:00:00
abstract：:In bacteria, disassembly of the ribosome at the end of translation is facilitated by an essential protein factor termed ribosome recycling factor (RRF), which works in concert with elongation factor G. Here we describe the crystal structure of the Thermus thermophilus RRF bound to a 70S ribosomal complex containing a ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1282
更新日期：2007-08-01 00:00:00
abstract：:The nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs undergoing premature termination of translation. It has been argued that in human cells, NMD is restricted to a pioneer round of translation initiated on mRNAs associated with the cap-binding complex (CBC) and that the exchange of the CBC for the eIF4F tran...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2575
更新日期：2013-06-01 00:00:00
abstract：:The typical function of kinesins is to transport cargo along microtubules. Binding of ATP to microtubule-attached motile kinesins leads to cargo displacement. To better understand the nature of the conformational changes that lead to the power stroke that moves a kinesin's load along a microtubule, we determined the X...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2624
更新日期：2013-08-01 00:00:00
abstract：:In eukaryotic cells, many introns are constitutively, rather than alternatively, spliced and therefore do not contribute to isoform diversification. It has remained unclear what functional roles such constitutive splicing provides. To explore this issue, we asked how splicing affects the efficiency with which individu...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/s41594-019-0226-x
更新日期：2019-06-01 00:00:00
abstract：:Spliceosomes catalyze the maturation of precursor mRNAs in organisms ranging from yeast to humans. Their catalytic core comprises three small nuclear RNAs (U2, U5 and U6) involved in substrate positioning and catalysis. It has been postulated, but never shown experimentally, that the U2-U6 complex adopts at least two ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1672
更新日期：2009-11-01 00:00:00
abstract：:BAK and BAX are essential mediators of apoptosis that oligomerize in response to death cues, thereby causing permeabilization of the mitochondrial outer membrane. Their transition from quiescent monomers to pore-forming oligomers involves a well-characterized symmetric dimer intermediate. However, no essential seconda...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/s41594-020-0494-5
更新日期：2020-11-01 00:00:00
abstract：:Lipoteichoic acids (LTAs) are essential cell-wall components in Gram-positive bacteria, including the human pathogen Staphylococcus aureus, contributing to cell adhesion, cell division and antibiotic resistance. Genetic evidence has suggested that LtaA is the flippase that mediates the translocation of the lipid-linke...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/s41594-020-0425-5
更新日期：2020-06-01 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：:An increasing body of evidence indicates that transcription and splicing are coupled, and it is accepted that chromatin organization regulates transcription. Little is known about the cross-talk between chromatin structure and exon-intron architecture. By analysis of genome-wide nucleosome-positioning data sets from h...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1659
更新日期：2009-09-01 00:00:00
abstract：:Telomeres may regulate human disease by at least two independent mechanisms. First, replicative senescence occurs once short telomeres generate DNA-damage signals that produce a barrier to tumor progression. Second, telomere position effects (TPE) could change gene expression at intermediate telomere lengths in cultur...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2571
更新日期：2013-06-01 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：:How do the key features of protein folding, elucidated from studies on native, isolated proteins, manifest in cotranslational folding on the ribosome? Using a well-characterized family of homologous α-helical proteins with a range of biophysical properties, we show that spectrin domains can fold vectorially on the rib...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.3355
更新日期：2017-03-01 00:00:00
abstract：:The iota toxin produced by Clostridium perfringens type E is a binary toxin comprising two independent polypeptides: Ia, an ADP-ribosyltransferase, and Ib, which is involved in cell binding and translocation of Ia across the cell membrane. Here we report cryo-EM structures of the translocation channel Ib-pore and its ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/s41594-020-0388-6
更新日期：2020-03-01 00:00:00
abstract：:Human telomeres are associated with ATM and the protein complex consisting of MRE11, RAD50 and NBS1 (MRN), which are central to maintaining genomic stability. Here we show that when targeted to telomeres, wild-type RAD50 downregulates telomeric association of TRF1, a negative regulator of telomere maintenance. TRF1 bi...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1286
更新日期：2007-09-01 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：:HIV-1 capsid plays multiple key roles in viral replication, and inhibition of capsid assembly is an attractive target for therapeutic intervention. Here, we report the atomic-resolution structure of capsid protein (CA) tubes, determined by magic-angle spinning NMR and data-guided molecular dynamics simulations. Functi...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/s41594-020-0489-2
更新日期：2020-09-01 00:00:00
abstract：:Expansion of CAG/CTG trinucleotide repeats is associated with certain familial neurological disorders, including Huntington's disease. Increasing evidence suggests that formation of a stable DNA hairpin within CAG/CTG repeats during DNA metabolism contributes to their expansion. However, the molecular mechanism(s) by ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1638
更新日期：2009-08-01 00:00:00
abstract：:Nuclear export of preribosomal subunits is a key step during eukaryotic ribosome formation. To efficiently pass through the FG-repeat meshwork of the nuclear pore complex, the large pre-60S subunit requires several export factors. Here we describe the mechanism of recruitment of the Saccharomyces cerevisiae RNA-export...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.3312
更新日期：2016-12-01 00:00:00
abstract：:Many aspects of nucleic acid metabolism, such as DNA replication, repair and transcription, are regulated by the post-translational modifiers ubiquitin and SUMO. Not surprisingly, DNA itself plays an integral part in determining the modification of most chromatin-associated targets. Conversely, ubiquitination or SUMOy...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章,评审
doi：10.1038/nsmb.2805
更新日期：2014-04-01 00:00:00
abstract：:The long noncoding RNA Xist is expressed from only the paternal X chromosome in mouse preimplantation female embryos and mediates transcriptional silencing of that chromosome. In females, absence of Xist leads to postimplantation lethality. Here, through single-cell RNA sequencing of early preimplantation mouse embryo...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.3365
更新日期：2017-03-01 00:00:00
