Abstract:
:Despite the great potential of RNAi, ectopic expression of shRNA or siRNAs holds the inherent risk of competition for critical RNAi components, thus altering the regulatory functions of some cellular microRNAs. In addition, specific siRNA sequences can potentially hinder incorporation of other siRNAs when used in a combinatorial approach. We show that both synthetic siRNAs and expressed shRNAs compete against each other and with the endogenous microRNAs for transport and for incorporation into the RNA induced silencing complex (RISC). The same siRNA sequences do not display competition when expressed from a microRNA backbone. We also show that TAR RNA binding protein (TRBP) is one of the sensors for selection and incorporation of the guide sequence of interfering RNAs. These findings reveal that combinatorial siRNA approaches can be problematic and have important implications for the methodology of expression and use of therapeutic interfering RNAs.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Castanotto D,Sakurai K,Lingeman R,Li H,Shively L,Aagaard L,Soifer H,Gatignol A,Riggs A,Rossi JJdoi
10.1093/nar/gkm543subject
Has Abstractpub_date
2007-01-01 00:00:00pages
5154-64issue
15eissn
0305-1048issn
1362-4962pii
gkm543journal_volume
35pub_type
杂志文章abstract::Poly 2'0-ethylcytidylic acid (poly (Ce)) was prepared by polymerization of 2'-0-ethylcytidine-5'-pyrophosphate with Escherichia coli polynucleotide phosphorylase in the presence of Mn++, and its properties compared with those of poly (rC), poly (Cm) and poly (dC). The neutral form of pOLY (Ce) exhibits properties simi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/3.3.817
更新日期:1976-03-01 00:00:00
abstract::Loss-of-function (LOF) methods such as RNA interference (RNAi), antisense oligonucleotides or CRISPR-based genome editing provide unparalleled power for studying the biological function of genes of interest. However, a major concern is non-specific targeting, which involves depletion of transcripts other than those in...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky437
更新日期:2018-07-06 00:00:00
abstract::The chromatin structure of a germ-line specific gene, the TPG-3 gene, one of the rainbow trout protamine genes was analyzed in various tissues. The protamine genes are expressed in early stage testis but not in late stage testis, liver or erythrocyte. Five potential CpG methylation sites in the coding and flanking reg...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/15.8.3385
更新日期:1987-04-24 00:00:00
abstract::BRCA1 expression is repressed by aberrant cytosine methylation in sporadic breast cancer. We hypothesized that aberrant cytosine methylation of the BRCA1 promoter was associated with the transcriptionally repressive effects of histone hypoacetylation and chromatin condensation. To address this question, we developed a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/28.17.3233
更新日期:2000-09-01 00:00:00
abstract::A DNA region of 2750 base pairs encompassing the genes III, VI and I of bacteriophage M13 has been sequenced by the Maxam-Gilbert procedure. By establishing the nucleotide changes introduced by several amber mutations, the coding region and the regulatory signals of each gene have been deduced. The genes appear to spa...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/6.8.2799
更新日期:1979-06-25 00:00:00
abstract::In this paper we develop a new method for genotyping Affymetrix single nucleotide polymorphism (SNP) array. The method is based on (i) using multiple arrays at the same time to determine the genotypes and (ii) a model that relates intensities of individual SNPs to each other. The latter point allows us to annotate SNP...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl475
更新日期:2006-01-01 00:00:00
abstract::MicroRNA (miRNA) 5'-isoforms, or 5'-isomiRs, are small-RNA species that originate from the same genomic loci as the major miRNAs with their 5' ends shifted from the 5' ends of the miRNAs by a few nucleotides. Although 5'-isomiRs have been reported, their origins, properties and potential functions remain to be examine...
journal_title:Nucleic acids research
pub_type: 杂志文章,meta分析
doi:10.1093/nar/gkt967
更新日期:2014-02-01 00:00:00
abstract::The rpoH genes encoding homologs of Escherichia coli sigma 32 (heat shock sigma factor) were isolated and sequenced from five gram negative proteobacteria (gamma or alpha subgroup): Enterobacter cloacae (gamma), Serratia marcescens (gamma), Proteus mirabilis (gamma), Agrobacterium tumefaciens (alpha) and Zymomonas mob...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:
更新日期:1995-11-11 00:00:00
abstract::Genomic imbalances are a major cause of constitutional and acquired disorders. Therefore, aneuploidy screening has become the cornerstone of preimplantation, prenatal and postnatal genetic diagnosis, as well as a routine aspect of the diagnostic workup of many acquired disorders. Recently, array comparative genomic hy...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl336
更新日期:2006-05-12 00:00:00
abstract::Epigenetics, and more specifically DNA methylation is a fast evolving research area. In almost every cancer type, each month new publications confirm the differentiated regulation of specific genes due to methylation and mention the discovery of novel methylation markers. Therefore, it would be extremely useful to hav...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm788
更新日期:2008-01-01 00:00:00
abstract::Peptide nucleic acids (PNAs) can bind to homopurine/homopyrimidine sequences of double-stranded DNA targets in a sequence-specific manner and form [PNA]2/DNA triplexes with single-stranded DNA D-loop structures at the PNA binding sites. These D-loop structures have been found to have a capacity to initiate transcripti...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/27.13.2806
更新日期:1999-07-01 00:00:00
abstract::The current pandemic situation caused by the Betacoronavirus SARS-CoV-2 (SCoV2) highlights the need for coordinated research to combat COVID-19. A particularly important aspect is the development of medication. In addition to viral proteins, structured RNA elements represent a potent alternative as drug targets. The s...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa1013
更新日期:2020-12-16 00:00:00
abstract::PASMet (Prediction, Analysis and Simulation of Metabolic networks) is a web-based platform for proposing and verifying mathematical models to understand the dynamics of metabolism. The advantages of PASMet include user-friendliness and accessibility, which enable biologists and biochemists to easily perform mathematic...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw415
更新日期:2016-07-08 00:00:00
abstract::The nucleotide sequences of the LTRs and their adjacent regions from 19 type C and one type B retrovirus were compared. Salient features are: (a) The R regions in the genomes of most of the type C retroviruses begin with GC and end with CA. (b) The mammalian type C retroviruses have a polyadenylation signal "AATAAA" i...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/12.4.1767
更新日期:1984-02-24 00:00:00
abstract::Sequence specific DNA methylation sometimes results in the protection of some or all of a restriction endonucleases' cleavage sites. This is usually, but not always, the result of methylation of one or both strands of DNA at the site characteristic of the corresponding "cognate" modification methylase. The known effec...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/9.22.5859
更新日期:1981-11-25 00:00:00
abstract::Search of interrelationships between the structural-functional protein organization and exon structure of encoding gene provides insights into issues concerned with the function, origin and evolution of genes and proteins. The functions of proteins and their domains are defined mostly by functional sites. The relation...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr1187
更新日期:2012-01-01 00:00:00
abstract::ExPASy (http://www.expasy.org) has worldwide reputation as one of the main bioinformatics resources for proteomics. It has now evolved, becoming an extensible and integrative portal accessing many scientific resources, databases and software tools in different areas of life sciences. Scientists can henceforth access s...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks400
更新日期:2012-07-01 00:00:00
abstract::T1DBase (http://www.t1dbase.org) is web platform, which supports the type 1 diabetes (T1D) community. It integrates genetic, genomic and expression data relevant to T1D research across mouse, rat and human and presents this to the user as a set of web pages and tools. This update describes the incorporation of new dat...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq912
更新日期:2011-01-01 00:00:00
abstract::A growing body of evidence suggests that genes transcribed by RNA polymerase III exhibit multiple functions within a chromosome. While the predominant function of these genes is the synthesis of RNA molecules, certain RNA polymerase III genes also function as genomic landmarks. Transfer RNA genes are known to exhibit ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh858
更新日期:2004-09-30 00:00:00
abstract::Characterization of the ability of human interferons (IFNs) to rapidly induce genes led to the identification of the first two members of the STAT (signal transducers and activators of transcription) family, Stat1 and Stat2. To study the unique role of this transcription factor in IFN signaling under more physiologica...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/27.21.4191
更新日期:1999-11-01 00:00:00
abstract::X chromosome inactivation results in the cis-limited inactivation of most, but not all, genes on one of the two X chromosomes in mammalian females. The molecular basis for inactivation is unknown. In order to examine the transcriptional activity of human X-linked genes, a series of mouse-human somatic cell hybrids und...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/18.14.4191
更新日期:1990-07-25 00:00:00
abstract::Minigenes encoding the peptide Met-Arg-Arg have been used to study the mechanism of toxicity of AGA codons proximal to the start codon or prior to the termination codon in bacteria. The codon sequences of the 'mini-ORFs' employed were initiator, combinations of AGA and CGA, and terminator. Both, AGA and CGA are low-us...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh784
更新日期:2004-08-18 00:00:00
abstract::Recently published alignments of available 5 S rRNA sequences have shown that a rigid base pairing pattern, pointing to the existence of a universal five-helix secondary structure for all 5 S RNAs, can be superimposed on such alignments. For a few species, the alignment and the base pairing pattern show distortions wi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/11.5.1245
更新日期:1983-03-11 00:00:00
abstract::The infection of Pseudomonas aeruginosa by the giant bacteriophage phiKZ is resistant to host RNA polymerase (RNAP) inhibitor rifampicin. phiKZ encodes two sets of polypeptides that are distantly related to fragments of the two largest subunits of cellular multisubunit RNAPs. Polypeptides of one set are encoded by mid...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv1095
更新日期:2015-12-02 00:00:00
abstract::Biological networks play increasingly important roles in omics data integration and systems biology. Over the past decade, many excellent tools have been developed to support creation, analysis and visualization of biological networks. However, important limitations remain: most tools are standalone programs, the majo...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky510
更新日期:2018-07-02 00:00:00
abstract::The Mouse Genome Database (MGD, http://www.informatics.jax.org/), integrates genetic, genomic and phenotypic information about the laboratory mouse, a primary animal model for studying human biology and disease. Information in MGD is obtained from diverse sources, including the scientific literature and external datab...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn886
更新日期:2009-01-01 00:00:00
abstract::Improving the accuracy of prediction of gene starts is one of a few remaining open problems in computer prediction of prokaryotic genes. Its difficulty is caused by the absence of relatively strong sequence patterns identifying true translation initiation sites. In the current paper we show that the accuracy of gene s...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.12.2607
更新日期:2001-06-15 00:00:00
abstract::Ribosome biogenesis is a dynamic multistep process, many features of which are still incompletely documented. Here, we show that changes in this pathway can be captured and annotated by means of a graphic set of pre-rRNA ratios, a technique we call Ratio Analysis of Multiple Precursors (RAMP). We find that knocking do...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gku787
更新日期:2014-01-01 00:00:00
abstract::The G- and U-specific reagent, carbodiimide was used to probe the solution structure of aminoacylated yeast phenylalanine tRNA. Both quantitative and qualitative changes in modification were observed when the modification patterns of tRNA-CCA(3'OH), tRNA-CCA(3'NH2) and phe-tRNA-CCA(3'NH2) were compared. Five nucleotid...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/10.7.2419
更新日期:1982-04-10 00:00:00
abstract::Algae are a diverse, polyphyletic group of photosynthetic eukaryotes spanning nearly all eukaryotic lineages of life and collectively responsible for ∼50% of photosynthesis on Earth. Sequenced algal genomes, critical to understanding their complex biology, are growing in number and require efficient tools for analysis...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa898
更新日期:2021-01-08 00:00:00