Abstract:
:Several authors have suggested or inferred that modest changes in microRNA expression can potentiate or impinge on their capacity to mediate gene repression, and that doing so could play a significant role in diseases. Such interpretations are based on several assumptions, namely: (i) changes in microRNA expression correlate with changes in the availability of mature, functional miRISC, (ii) changes in microRNA expression can significantly alter the stoichiometry of miRISC populations with their cognate targets, (iii) and this, in turn, can result in changes in miRISC silencing output. Here, we experimentally challenge those assumptions by quantifying and altering the availability of miRISC across several families of microRNAs. Doing so revealed a surprising fragmentation in the miRISC functional pool, striking differences in the availability of miRNA families and saturability of miRNA-mediated silencing. Furthermore, we provide direct experimental evidence that only a limited subset of miRNAs, defined by a conjuncture of expression threshold, miRISC availability and low target site abundance, is susceptible to competitive effects through microRNA-binding sites.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Mayya VK,Duchaine TFdoi
10.1093/nar/gkv720subject
Has Abstractpub_date
2015-09-03 00:00:00pages
7556-65issue
15eissn
0305-1048issn
1362-4962pii
gkv720journal_volume
43pub_type
杂志文章abstract::We present FIGfams, a new collection of over 100,000 protein families that are the product of manual curation and close strain comparison. Using the Subsystem approach the manual curation is carried out, ensuring a previously unattained degree of throughput and consistency. FIGfams are based on over 950,000 manually a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp698
更新日期:2009-11-01 00:00:00
abstract::DNA, isolated from age-synchronous senescent populations of Caenorhabditis elegans has been quantitatively and qualitatively analyzed for the presence of 5-methylcytosine. High performance liquid chromatography on two wild-type and several mutant strains of C. elegans failed to detect any 5-methylcytosine. The restric...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/14.16.6711
更新日期:1986-08-26 00:00:00
abstract::For the isolation of single stranded plasmid DNA, various E. coli and E. coli-Streptomyces shuttle plasmids were equipped with the phage f1 replication origin. The transformation of some representative Streptomyces species with plasmid vectors occurred irrespective of whether single or double stranded DNA was used. In...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/19.4.727
更新日期:1991-02-25 00:00:00
abstract::Although many tools have been developed to analyze small RNA sequencing (sRNA-Seq) data, it remains challenging to accurately analyze the small RNA population, mainly due to multiple sequence ID assignment caused by short read length. Additional issues in small RNA analysis include low consistency of microRNA (miRNA) ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx999
更新日期:2017-12-01 00:00:00
abstract::Naturally occurring RNAs are known to exhibit a high degree of modularity, whereby specific structural modules (or motifs) can be mixed and matched to create new molecular architectures. The modular nature of RNA also affords researchers the ability to characterize individual structural elements in controlled syntheti...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz304
更新日期:2019-07-09 00:00:00
abstract::Telomerase is a ribonucleoprotein reverse transcriptase that synthesizes and maintains telomeric DNA. Studies of telomeres and telomerase are facilitated by the large number of linear DNA molecules found in ciliated protozoa, such as Tetrahymena thermophila. To examine the expression of telomerase, we investigated the...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/27.21.4269
更新日期:1999-11-01 00:00:00
abstract::Regulatory T-cells (Treg) play an essential role in the negative regulation of immune answers by developing an attenuated cytokine response that allows suppressing proliferation and effector function of T-cells (CD4(+) Th). The transcription factor FoxP3 is responsible for the regulation of many genes involved in the ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr444
更新日期:2011-10-01 00:00:00
abstract::We report the extended database and data mining resources newly released in the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). H-InvDB is a comprehensive annotation resource of human genes and transcripts, and consists of two main views and six sub-databases. The latest release of H-InvDB (release 6...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp1020
更新日期:2010-01-01 00:00:00
abstract::A promoter with the potential to adopt a 50 basepair (bp) cruciform spanning from -19 to -69 has been constructed in the plasmid pBR322 tetracycline resistance gene (tet) by forming an inverted repeat from '-35' sequences. Compared to a control promoter, the sequence of this cruciform promoter differs only by a 22 bp ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/17.14.5537
更新日期:1989-07-25 00:00:00
abstract::A novel program suite was implemented for the functional interpretation of high-throughput gene expression data based on the identification of Gene Ontology (GO) nodes. The focus of the analysis lies on the interpretation of microarray data from prokaryotes. The three well established statistical methods of the thresh...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl329
更新日期:2006-07-01 00:00:00
abstract::Plant viruses ubiquitously mediate the induction of miR168 trough the activities of viral suppressors of RNA silencing (VSRs) controlling the accumulation of ARGONAUTE1 (AGO1), one of the main components of RNA silencing based host defence system. Here we used a mutant Tombusvirus p19 VSR (p19-3M) disabled in its main...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt846
更新日期:2014-01-01 00:00:00
abstract::Diastereomeric dithymidine methanephosphonamidates (TnpmT) were synthesized by reaction of 3'-amino-3'-deoxythymidine with 3'- O -acetylthymidin-5-yl-methanephosphonochloridate. Separated dinucleotide TnpmT(fast) and TnpmT(slow) diastereomers were used as building blocks to prepare chimeric dodecathy-midylates, posses...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.11.2650
更新日期:1998-06-01 00:00:00
abstract::More and more evidences demonstrate that the long non-coding RNAs (lncRNAs) play many key roles in diverse biological processes. There is a critical need to annotate the functions of increasing available lncRNAs. In this article, we try to apply a global network-based strategy to tackle this issue for the first time. ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks967
更新日期:2013-01-01 00:00:00
abstract::An immunofluorescence assay was developed to identify proteins specifically binding to oligonucleoside phosphorodithioate (ODN) aptamers from a bead-bound ODN library. Accordingly, NF-kappaB p50 protein was incubated with either bead-bound NF-kappaB consensus sequence or a bead-bound ODN combinatorial library and adso...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gng054
更新日期:2003-05-15 00:00:00
abstract::The small proline-rich protein genes ( SPRRs ) code for precursors of the cornified cell envelope, and are specifically expressed during keratinocyte terminal differentiation. The single intron of SPRR2A enhanced the activity of the SPRR2A promoter in transient transfection assays. This enhancement was position depend...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.23.5288
更新日期:1998-12-01 00:00:00
abstract::A sixty base pair DNA duplex containing the nucleotide sequence of the bacteriophage T5 early (T5P25) promoter has been constructed using a combination of chemical synthesis and enzymatic methods. Subsequent to cloning into pBR322, the promoter has been demonstrated to be biologically active being capable of directing...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/11.17.5921
更新日期:1983-09-10 00:00:00
abstract::Galahad (https://galahad.esat.kuleuven.be) is a web-based application for analysis of drug effects. It provides an intuitive interface to be used by anybody interested in leveraging microarray data to gain insights into the pharmacological effects of a drug, mainly identification of candidate targets, elucidation of m...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv436
更新日期:2015-07-01 00:00:00
abstract::Two analog uridine triphosphates tethering additional functionality, one a primary amino group and the second a mercapto group, were prepared and tested for their compatibility with in vitro RNA selection procedures. 5-(3-Aminopropyl)uridine triphosphate (UNH(2)) as a uridine substitute was a more effective substrate ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/28.17.3316
更新日期:2000-09-01 00:00:00
abstract::GAP-43 is a membrane phosphoprotein that is important for the development and plasticity of neural connections. In undifferentiated PC12 pheochromocytoma cells, GAP-43 mRNA degrades rapidly ( t = 5 h), but becomes stable when cells are treated with nerve growth factor. To identify trans- acting factors that may influe...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/25.6.1281
更新日期:1997-03-15 00:00:00
abstract::The high-throughput sequencing of nuclease-protected mRNA fragments bound to ribosomes, a technique known as ribosome profiling, quantifies the relative frequencies with which different regions of transcripts are translated. This technique has revealed novel translation initiation sites with unprecedented scope and ha...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv200
更新日期:2015-04-20 00:00:00
abstract::Deamination of cytosine (C), 5-methylcytosine (mC) and 5-hydroxymethylcytosine (hmC) occurs spontaneously in mammalian DNA with several hundred deaminations occurring in each cell every day. The resulting potentially mutagenic mispairs of uracil (U), thymine (T) or 5-hydroxymethyluracil (hmU) with guanine (G) are subs...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks259
更新日期:2012-07-01 00:00:00
abstract::Targeted delivery of antisense oligonucleotides (ASO) to hepatocytes via the asialoglycoprotein receptor (ASGR) has improved the potency of ASO drugs ∼30-fold in the clinic (1). In order to fully characterize the effect of GalNAc valency, oligonucleotide length, flexibility and chemical composition on ASGR binding, we...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx060
更新日期:2017-03-17 00:00:00
abstract::Phosphoprotein-binding domains (PPBDs) mediate many important cellular and molecular processes. Ten PPBDs have been known to exist in the human proteome, namely, 14-3-3, BRCT, C2, FHA, MH2, PBD, PTB, SH2, WD-40 and WW. PepCyber:P approximately PEP is a newly constructed database specialized in documenting human PPBD-c...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm854
更新日期:2008-01-01 00:00:00
abstract::SITEHOUND-web (http://sitehound.sanchezlab.org) is a binding-site identification server powered by the SITEHOUND program. Given a protein structure in PDB format SITEHOUND-web will identify regions of the protein characterized by favorable interactions with a probe molecule. These regions correspond to putative ligand...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp281
更新日期:2009-07-01 00:00:00
abstract::An elongation cycle of a transcribing RNA polymerase (RNAP) usually consists of multiple kinetics steps, so there exist multiple kinetic checkpoints where non-cognate nucleotides can be selected against. We conducted comprehensive free energy calculations on various nucleotide insertions for viral T7 RNAP employing al...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz213
更新日期:2019-05-21 00:00:00
abstract::Using peptide arrays and binding to native histone proteins, we show that the ADD domain of Dnmt3a specifically interacts with the H3 histone 1-19 tail. Binding is disrupted by di- and trimethylation of K4, phosphorylation of T3, S10 or T11 and acetylation of K4. We did not observe binding to the H4 1-19 tail. The ADD...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq147
更新日期:2010-07-01 00:00:00
abstract::Telomere G-quadruplex is emerging as a promising anti-cancer target due to its inhibition to telomerase, an enzyme expressed in more than 85% tumors. Telomerase-mediated telomere extension and some other reactions require a free 3' telomere end in single-stranded form. G-quadruplex formation near the 3' end of telomer...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr164
更新日期:2011-08-01 00:00:00
abstract::Vaccinia virus DNA topoisomerase catalyzes resolution of synthetic Holliday junctions in vitro. The mechanism entails concerted transesterifications at two recognition sites, 5'-CCCTT/, that are opposed within a partially mobile four-way junction. Efficient resolution occurs on a junction with a 10 bp segment of branc...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/28.14.2658
更新日期:2000-07-15 00:00:00
abstract::We constructed several deletion mutants of Escherichia coli single-stranded DNA binding protein (EcoSSB) lacking different parts of the C-terminal region. This region of EcoSSB is composed of two parts: a glycine and proline-rich sequence of approximately 60 amino acids followed by an acidic region of the last 10 amin...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.14.2706
更新日期:1996-07-15 00:00:00
abstract::The mouse is widely used as system to study human genetic mechanisms. However, extensive rewiring of transcriptional regulatory networks often confounds translation of findings between human and mouse. Site-specific gain and loss of individual transcription factor binding sites (TFBS) has caused functional divergence ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky018
更新日期:2018-02-28 00:00:00