Abstract:
:MicroRNAs (miRNAs) interact with target sites located in the 3' untranslated regions (3' UTRs) of mRNAs to downregulate their expression when the appropriate miRNA is bound to target mRNA. To establish the functional importance of target-site localization in the 3' UTR, we modified the stop codon to extend the coding region of the transgene reporter through the miRNA target sequence. As a result, the miRNAs lost their ability to inhibit translation but retained their ability to function as small interfering RNAs in mammalian cells in culture and in vivo. The addition of rare but not optimal codons upstream of the extended opening reading frame (ORF) made the miRNA target site more accessible and restored miRNA-induced translational knockdown. Taken together, these results suggest that active translation impedes miRNA-programmed RISC association with target mRNAs and support a mechanistic explanation for the localization of most miRNA target sites in noncoding regions of mRNAs in mammals.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Gu S,Jin L,Zhang F,Sarnow P,Kay MAdoi
10.1038/nsmb.1552subject
Has Abstractpub_date
2009-02-01 00:00:00pages
144-50issue
2eissn
1545-9993issn
1545-9985pii
nsmb.1552journal_volume
16pub_type
杂志文章abstract::We have isolated a soluble cytochrome from Shewanella oneidensis that contains eight covalently attached heme groups and determined its crystal structure. One of these hemes exhibits novel ligation of the iron atom by the epsilon-amino group of a lysine residue, despite its attachment via a typical CXXCH motif. This h...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb827
更新日期:2004-10-01 00:00:00
abstract::Bacteriophage T4 and related viruses have a contractile tail that serves as an efficient mechanical device for infecting bacteria. A three-dimensional cryo-EM reconstruction of the mature T4 tail assembly at 15-A resolution shows the hexagonal dome-shaped baseplate, the extended contractile sheath, the long tail fiber...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb975
更新日期:2005-09-01 00:00:00
abstract::Myosin V is a double-headed processive molecular motor that moves along an actin filament by taking 36-nm steps. Using optical trapping nanometry with high spatiotemporal resolution, we discovered that there are two possible pathways for the 36-nm steps, one with 12- and 24-nm substeps, in this order, and the other wi...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb806
更新日期:2004-09-01 00:00:00
abstract::Primary microRNA cleavage by the Drosha-Dgcr8 'Microprocessor' complex is critical for microRNA biogenesis. Yet, the Microprocessor may also cleave other nuclear RNAs in a nonspecific manner. We studied Microprocessor function using mathematical modeling and experiments in mouse and human tissues. We found that the au...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2293
更新日期:2012-05-13 00:00:00
abstract::The monoclonal antibody 13H11 shares part of its epitope in the HIV-1 gp41 membrane-proximal external region (MPER) with the rare, broadly neutralizing human antibody 2F5. Although 13H11 partially cross-blocked 2F5 binding, 13H11 is non-neutralizing and does not block 2F5 neutralization. We show that unlike 2F5, 13H11...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1944
更新日期:2010-12-01 00:00:00
abstract::Flavin-containing monooxygenases (FMOs) are ubiquitous in all domains of life and metabolize a myriad of xenobiotics, including toxins, pesticides and drugs. However, despite their pharmacological importance, structural information remains bereft. To further our understanding behind their biochemistry and diversity, w...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-019-0347-2
更新日期:2020-01-01 00:00:00
abstract::Ribosomes catalyze the formation of peptide bonds between aminoacyl esters of transfer RNAs within a catalytic center composed of ribosomal RNA only. Here we show that the reaction of P-site formylmethionine (fMet)-tRNA(fMet) with a modified A-site tRNA substrate, Phelac-tRNA(Phe), in which the nucleophilic amino grou...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb1091
更新日期:2006-05-01 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::Targeted gene silencing by RNA interference (RNAi) requires loading of a short guide RNA (small interfering RNA (siRNA) or microRNA (miRNA)) onto an Argonaute protein to form the functional center of an RNA-induced silencing complex (RISC). In humans, Argonaute2 (AGO2) assembles with the guide RNA-generating enzyme Di...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1673
更新日期:2009-11-01 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::Polycomb repressive complex 2 (PRC2) trimethylates histone H3 at lysine 27 to mark genes for repression. We measured the dynamics of PRC2 binding on recombinant chromatin and free DNA at the single-molecule level using total internal reflection fluorescence (TIRF) microscopy. PRC2 preferentially binds free DNA with mu...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.3488
更新日期:2017-12-01 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 N-terminal acetylation of Sir3 is essential for heterochromatin establishment and maintenance in yeast, but its mechanism of action is unknown. The crystal structure of the N-terminally acetylated BAH domain of Saccharomyces cerevisiae Sir3 bound to the nucleosome core particle reveals that the N-terminal acetylat...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2641
更新日期:2013-09-01 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
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::Integrins are heterodimeric cell-surface adhesion molecules comprising one of 18 possible α-chains and one of eight possible β-chains. They control a range of cell functions in a matrix- and ligand-specific manner. Integrins can be internalized by clathrin-mediated endocytosis (CME) through β subunit-based motifs foun...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.3161
更新日期:2016-02-01 00:00:00
abstract::The structure of the Sortilin ectodomain in complex with neurotensin has been determined at 2-A resolution, revealing that the C-terminal part of neurotensin binds in the tunnel of a ten-bladed beta-propeller domain. Binding competition studies suggest that additional binding sites, for example, for the prodomain of n...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1543
更新日期:2009-01-01 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::Desensitization is a universal feature of ligand-gated ion channels. Using the crystal structure of the GluR2 L483Y mutant channel as a guide, we attempted to build non-desensitizing kainate-subtype glutamate receptors. Success was achieved for GluR5, GluR6 and GluR7 with intermolecular disulfide cross-links but not b...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb1178
更新日期:2006-12-01 00:00:00
abstract::The cocrystal structure of the PP7 bacteriophage coat protein in complex with its translational operator identifies a distinct mode of sequence-specific RNA recognition when compared to the well-characterized MS2 coat protein-RNA complex. The structure reveals the molecular basis of the PP7 coat protein's ability to s...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb1327
更新日期:2008-01-01 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::Suppressing cellular signal transducers of transcription 2 (STAT2) is a common strategy that viruses use to establish infections, yet the detailed mechanism remains elusive, owing to a lack of structural information about the viral-cellular complex involved. Here, we report the cryo-EM and crystal structures of human ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-020-0472-y
更新日期:2020-10-01 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::The Mre11-Rad50-NBS1 (MRN) complex has many roles in response to DNA double-strand breaks, but its functions in repair by nonhomologous end joining (NHEJ) pathways are poorly understood. We have investigated requirements for MRN in class switch recombination (CSR), a programmed DNA rearrangement in B lymphocytes that ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1639
更新日期:2009-08-01 00:00:00
abstract:: ...
journal_title:Nature structural & molecular biology
pub_type: 新闻
doi:10.1038/s41594-018-0066-0
更新日期:2018-06-01 00:00:00
abstract::Allosteric interactions are typically considered to proceed through a series of discrete changes in bonding interactions that alter the protein conformation. Here we show that allostery can be mediated exclusively by transmitted changes in protein motions. We have characterized the negatively cooperative binding of cA...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb1132
更新日期:2006-09-01 00:00:00
abstract::Platelet-activating-factor receptor (PAFR) responds to platelet-activating factor (PAF), a phospholipid mediator of cell-to-cell communication that exhibits diverse physiological effects. PAFR is considered an important drug target for treating asthma, inflammation and cardiovascular diseases. Here we report crystal s...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-018-0068-y
更新日期:2018-06-01 00:00:00
abstract::When targeting promoter regions, small interfering RNAs (siRNAs) trigger a previously proposed pathway known as transcriptional gene silencing by promoting heterochromatin formation. Here we show that siRNAs targeting intronic or exonic sequences close to an alternative exon regulate the splicing of that exon. The eff...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1620
更新日期:2009-07-01 00:00:00
abstract::Tripeptidyl peptidase II (TPP II) is the largest known eukaryotic protease (6 MDa). It is believed to act downstream of the 26S proteasome, cleaving tripeptides from the N termini of longer peptides, and it is implicated in numerous cellular processes. Here we report the structure of Drosophila TPP II determined by a ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1870
更新日期:2010-08-01 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