Abstract:
:Identifying the downstream targets of microRNAs (miRNAs) is essential to understanding cellular regulatory networks. We devised a direct biochemical method for miRNA target discovery that combined RNA-induced silencing complex (RISC) purification with microarray analysis of bound mRNAs. Because targets of miR-124a have been analyzed, we chose it as our model. We honed our approach both by examining the determinants of stable binding between RISC and synthetic target RNAs in vitro and by determining the dependency of both repression and RISC coimmunoprecipitation on miR-124a seed sites in two of its well characterized targets in vivo. Examining the complete spectrum of miR-124 targets in 293 cells yielded both a set that were down-regulated at the mRNA level, as previously observed, and a set whose mRNA levels were unaffected by miR-124a. Reporter assays validated both classes, extending the spectrum of mRNA targets that can be experimentally linked to the miRNA pathway.
journal_name
Proc Natl Acad Sci U S Aauthors
Karginov FV,Conaco C,Xuan Z,Schmidt BH,Parker JS,Mandel G,Hannon GJdoi
10.1073/pnas.0709971104subject
Has Abstractpub_date
2007-12-04 00:00:00pages
19291-6issue
49eissn
0027-8424issn
1091-6490pii
0709971104journal_volume
104pub_type
杂志文章abstract::Single-copy transgenes in Caenorhabditis elegans can be subjected to a potent, irreversible silencing process termed small RNA-induced epigenetic silencing (RNAe). RNAe is promoted by the Piwi Argonaute protein PRG-1 and associated Piwi-interacting RNAs (piRNAs), as well as by proteins that promote and respond to seco...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1501979112
更新日期:2015-05-19 00:00:00
abstract::Innate immunity is the primary and most ancient defense against infection. Although critical to survival, coordinating protection against a foreign organism is energetically costly, creating the need to reallocate substrates from nonessential functions, such as growth and nutrient storage. However, the mechanism by wh...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0906749106
更新日期:2009-12-08 00:00:00
abstract::A 1-hr exposure of bovine lenses in organ culture to H2O2 concentrations in the range found in the aqueous fluid of patients with cataracts inhibits 86Rb+ influx. At 1 mM H2O2, complete inhibition was observed and further investigated. Membrane permeability is slightly decreased. Although lactate concentrations increa...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.7.2044
更新日期:1983-04-01 00:00:00
abstract::To elucidate the function of the two nerve growth factor (NGF) receptors, p75NGFR and p140trk, chimeric molecules were constructed of tumor necrosis factor (TNF) and NGF receptors. Rat PC12 pheochromocytoma cells transiently transfected with TNF-p140trk chimeras, which contain the extracellular domain of TNF receptor ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.18.8717
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abstract::Myosin X (MyoX), encoded by Myo10, is a representative member of the MyTH4-FERM domain-containing myosins, and this family of unconventional myosins shares common functions in promoting formation of filopodia/stereocilia structures in many cell types with unknown mechanisms. Here, we present the structure of the MyoX ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1016567108
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1220710110
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abstract::Ribozyme activity in vivo depends on achieving high-level expression, intracellular stability, target colocalization, and cleavage site access. At present, target site selection is problematic because of unforeseeable secondary and tertiary RNA structures that prevent cleavage. To overcome this design obstacle, we wis...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.091411398
更新日期:2001-05-08 00:00:00
abstract::A complementarity-determining region (CDR) of the mouse monoclonal antibody (mAb) F58 was constructed with specificity to a neutralization-inducing region of human immunodeficiency virus type 1 (HIV-1). The mAb has its major reactivity to the amino acid sequence I--GPGRA in the V3 viral envelope region. All CDRs inclu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.10.4374
更新日期:1993-05-15 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.4.1611
更新日期:1990-02-01 00:00:00
abstract::Spleen cells derived from a rabbit hyperimmunized with a Type III pneumococcal vaccine were exposed to simian virus 40 in vitro. After 114 days, transformed cells growing on the surface of one culture dish were observed and a cell line was established. The transformed cells had a morphology characteristic of cells tra...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.71.2.260
更新日期:1974-02-01 00:00:00
abstract::The C terminus of transcription factor NusA from Escherichia coli comprises two repeat units, which bind during antitermination to protein N from phage lambda. To delineate the structural basis of the NusA-lambdaN interaction, we attempted to crystallize the NusA C-terminal repeats in complex with a lambdaN peptide (r...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0405883101
更新日期:2004-09-21 00:00:00
abstract::The U.S. case against Iran is based on Iran's deceptions regarding nuclear weapons development. This case is buttressed by assertions that a state so petroleum-rich cannot need nuclear power to preserve exports, as Iran claims. The U.S. infers, therefore, that Iran's entire nuclear technology program must pertain to w...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0603903104
更新日期:2007-01-02 00:00:00
abstract::In the chalcone synthase gene of Antirrhinum majus (snapdragon), 150 base pairs of the 5' flanking region contain cis-acting signals for UV light-induced expression. A nuclear factor, designated CG-1, specifically recognizes a hexameric motif with internal dyad symmetry, CACGTG, located within this light-responsive se...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.18.6930
更新日期:1989-09-01 00:00:00
abstract::Recent experiments have shown that mouse primary visual cortex (V1) is very different from that of cat or monkey, including response properties-one of which is that contrast invariance in the orientation selectivity (OS) of the neurons' firing rates is replaced in mouse with contrast-dependent sharpening (broadening) ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1719044115
更新日期:2018-11-06 00:00:00
abstract::Glycogenin initiates the synthesis of a maltosaccharide chain covalently attached to itself on Tyr195 via a stepwise glucosylation reaction, priming glycogen synthesis. We have captured crystallographic snapshots of human glycogenin during its reaction cycle, revealing a dynamic conformational switch between ground an...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1113921108
更新日期:2011-12-27 00:00:00
abstract::Xenogeneic monoclonal antibodies were prepared to the murine interleukin 2 (IL-2)-dependent HT2 cell line. One rat IgM monoclonal antibody (7D4) was identified that inhibited proliferation of the HT2 cells and of IL-2-dependent CTLL cells in the presence of crude rat IL-2 as well as of purified human IL-2. The level o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.18.5694
更新日期:1983-09-01 00:00:00
abstract::Lysinuric protein intolerance (LPI) is an autosomal recessive phenotype consistent with impaired transport of cationic amino acids at the basolateral membrane of intestinal and renal epithelia. On the assumption that the basolateral membrane of epithelial cells and plasma membrane of parenchymal cells are functional a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.21.7711
更新日期:1987-11-01 00:00:00
abstract::The accuracy of computer predictions of RNA secondary structure from sequence data and free energy parameters has been increased to roughly 70%. Performance is judged by comparison with structures known from phylogenetic analysis. The algorithm also generates suboptimal structures. On average, the best structure withi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.20.7706
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abstract::Increased DNA levels in centrally located endosperm nuclei are shown to be related to endosperm development in Zea mays. Mitotic activity sharply decreases in endosperm cells 10-12 days after pollination. At this time nuclear size and DNA content per nucleus (where C = haploid content) sharply increase until peak leve...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2011-04-12 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.21.8545
更新日期:1990-11-01 00:00:00
abstract::Citrullinemia is an inborn error of metabolism due to deficiency of the urea cycle enzyme, argininosuccinate synthetase [L-citrulline:L-aspartate ligase (AMP-forming), EC 6.3.4.5]. The disease was first described in humans but was recently reported in dairy cattle in Australia. Here we report the nucleotide sequence o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.20.7947
更新日期:1989-10-01 00:00:00
abstract::Pro-Leu-Gly-NH2 (MIF) and several structural analogues, all injected in 50-microgram doses daily in mice receiving morphine chronically, were found to prevent development of physical dependence as measured by changes in body temperature associated with naloxone-induced withdrawal. Dose-response studies, using again a ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:1979-01-01 00:00:00
abstract::Increased intestinal permeability has been observed in numerous human autoimmune diseases, including type-1 diabetes (T1D) and its' animal model, the BB-wor diabetic prone rat. We have recently described zonulin, a protein that regulates intercellular tight junctions. The objective of this study was to establish wheth...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0500178102
更新日期:2005-02-22 00:00:00
abstract::The DNA sequence of a tryptophan synthase gene and the flanking 5' and 3' regions has been determined for Arabidopsis thaliana. The sequence encodes only the beta subunit domain, indicating that alpha and beta subunits are specified by separate genes. The gene contains four introns and encodes 470 amino acid residues....
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.86.12.4604
更新日期:1989-06-01 00:00:00
abstract::Defining the virus-host interactions responsible for HIV-1 transmission, including the phenotypic requirements of viruses capable of establishing de novo infections, could be important for AIDS vaccine development. Previous analyses have failed to identify phenotypic properties other than chemokine receptor 5 (CCR5) a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2013-04-23 00:00:00
abstract::Over the past decade or more, contradictory evidence of Martian climate, indicating that surface temperatures seldom if ever approach the melting point of water at midlatitudes, and geomorphic features, consistent with liquid flows at these same latitudes, have proven difficult to reconcile. In this article, we demons...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0308251101
更新日期:2004-06-08 00:00:00
abstract::A ribosomal RNA-encoding DNA (rDNA) cloned sequence, consisting of a 0.8-kilobase fragment from the 26S/nontranscribed spacer region, was used to identify diagnostic restriction enzyme fragments that distinguish the Moreton and Torresian subspecies of the grasshopper Caledia captiva. These restriction fragments were t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.11.3946
更新日期:1987-06-01 00:00:00
abstract::The interaction of configurations, including all possible singly excited configurations, is incorporated into the calculation of oscillatory and rotatory intensities of simple nonplanar pi-electronic systems such as skewed butadiene and acrolein. The results are discussed in terms of the reliability of the (self-consi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.67.4.1727
更新日期:1970-12-01 00:00:00
abstract::Split GFPs have been widely applied for monitoring protein-protein interactions by expressing GFPs as two or more constituent parts linked to separate proteins that only fluoresce on complementing with one another. Although this complementation is typically irreversible, it has been shown previously that light acceler...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1618087114
更新日期:2017-03-14 00:00:00