Abstract:
:Strategies to regulate gene function frequently use small interfering RNAs (siRNAs) that can be made from their shRNA precursors via Dicer. However, when the duplex components of these siRNA effectors are expressed from their respective coding genes, the RNA interference (RNAi) activity is much reduced. Here, we explored the mechanisms of action of shRNA and siRNA and found the expressed siRNA, in contrast to short hairpin RNA (shRNA), exhibits strong strand antagonism, with the sense RNA negatively and unexpectedly regulating RNAi. Therefore, we altered the relative levels of strands of siRNA duplexes during their expression, increasing the level of the antisense component, reducing the level of the sense component, or both and, in this way we were able to enhance the potency of the siRNA. Such vector-delivered siRNA attacked its target effectively. These findings provide new insight into RNAi and, in particular, they demonstrate that strand antagonism is responsible for making siRNA far less potent than shRNA.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Jin X,Sun T,Zhao C,Zheng Y,Zhang Y,Cai W,He Q,Taira K,Zhang L,Zhou Ddoi
10.1093/nar/gkr927subject
Has Abstractpub_date
2012-02-01 00:00:00pages
1797-806issue
4eissn
0305-1048issn
1362-4962pii
gkr927journal_volume
40pub_type
杂志文章abstract::PKR is a doubled-stranded RNA-dependent protein kinase which is implicated in the regulation of several cellular processes, including cell proliferation. PKR undergoes phosphorylation and activation in mouse embryonic 3T3-F442A cells in response to endogenous RNA(s). Activation of PKR is related to growth and differen...
journal_title:Nucleic acids research
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abstract::In continuation with work regarding the evaluation of the energy of association of various RNA bases with various base pairs, the results of the computations of the electrostatic interaction energy of A-U base pair with four RNA bases viz. Adenine, Uracil, Guanine and Cytosine have been reported. Non bonded induced po...
journal_title:Nucleic acids research
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journal_title:Nucleic acids research
pub_type: 杂志文章
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journal_title:Nucleic acids research
pub_type: 杂志文章
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更新日期:2016-07-08 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/22.6.977
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abstract::The loss of the tumour suppressor E-cadherin (Cdh1) is a key event during tumourigenesis and epithelial-mesenchymal transition (EMT). Transforming growth factor-β (TGFβ) triggers EMT by inducing the expression of non-histone chromatin protein High Mobility Group A2 (HMGA2). We have previously shown that HMGA2, togethe...
journal_title:Nucleic acids research
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv1259
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gku1194
更新日期:2015-01-01 00:00:00
abstract::The Class 3 aldehyde dehydrogenase gene (ALDH-3) is differentially expressed. Expression is either constitutive or xenobiotic inducible via an aromatic hydrocarbon (Ah) receptor-mediated pathway, depending upon the tissue. A series of studies were performed to examine the regulation of rat ALDH-3 basal expression. DNa...
journal_title:Nucleic acids research
pub_type: 杂志文章
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz780
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt1321
更新日期:2014-03-01 00:00:00
abstract::The hypoxia-inducible factor-1 (HIF-1) was first described as a DNA binding activity that specifically recognizes an 8 bp motif known to be essential for hypoxia-inducible erythropoietin gene transcription. Subsequently HIF-1 activity has also been found in cell lines which do not express erythropoietin, suggesting th...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/23.22.4542
更新日期:1995-11-25 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/9.21.5811
更新日期:1981-11-11 00:00:00
abstract::DNA methylation, the most intensively studied epigenetic modification, plays an important role in understanding the molecular basis of diseases. Furthermore, epigenome-wide association study (EWAS) provides a systematic approach to identify epigenetic variants underlying common diseases/phenotypes. However, there is n...
journal_title:Nucleic acids research
pub_type: 杂志文章
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更新日期:2019-01-08 00:00:00
abstract::We had shown previously (3) that the E. coli argE gene could be turned-on by an IS3 element inserted in orientation II near the 5' end of the gene. Here we show that this effect is due to the presence of an outward promoter located on IS3. The exact site of insertion of IS3 was determined by DNA sequencing. Using the ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/10.19.5935
更新日期:1982-10-11 00:00:00
abstract::The modulation of GLI2, an oncogenic transcription factor commonly upregulated in cancer, is in many cases not due to genetic defects, suggesting dysregulation through alternative mechanisms. The identity of these molecular events remains for the most part unknown. Here, we identified TFII-I as a novel repressor of GL...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa476
更新日期:2020-07-27 00:00:00
abstract::Earlier studies in DNA self-assembly have foretold the feasibility of building addressable nanostructures with multi-stranded motifs, which is fully validated in this study. In realizing this feasibility in DNA nanotechnology, a diversified set of motifs of modified domain lengths is extended from a classic type. The ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx121
更新日期:2017-04-07 00:00:00
abstract::DNA lengths in the structural repeat units of Chinese hamster ovary (CHO) and chicken erythrocyte chromatin were compared by analyzing the sizes of DNA fragments produced after treatment of nuclei with staphylococcal nuclease. The repeat length of CHO chromatin (173 +- 4 BP) is about 20 base pairs (BP) smaller than th...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/4.4.771
更新日期:1977-04-01 00:00:00
abstract::In this paper, we report the cloning and sequencing of the C. elegans histidyl-tRNA synthetase gene. The complete genomic sequence, and most of the cDNA sequence, of this gene is now determined. The gene size including flanking and coding regions is 2230 nucleotides long. Three small introns (45-50 bp long) are found ...
journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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abstract::Human transcription factor Sp1 contains three contiguous repeats of the C2H2-type zinc finger motif and binds to the decanucleotide sequence 5'-(G/T)GGGCGG(G/A)(G/A)(C/T)-3' (GC box). In order to determine whether the three-zinc finger peptide Sp1(530-623) has selectivity for sequence outside the GC box, we used a sel...
journal_title:Nucleic acids research
pub_type: 杂志文章
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更新日期:2001-12-15 00:00:00
abstract::Aging research is a multi-disciplinary field encompassing knowledge from many areas of basic, applied and clinical research. Age-related processes occur on molecular, cellular, tissue, organ, system, organismal and even psychological levels, trigger the onset of multiple debilitating diseases and lead to a loss of fun...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv1287
更新日期:2016-01-04 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.3.469
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abstract::Here we report that the poor binding of methylphosphonate oligodeoxynucleosides (MP-ODNs) to their nucleic acid targets can be improved by additional inversion of the anomeric configuration (from beta to alpha) in the sugar moieties to give a new class of analogs, MP alpha-oligonucleosides. MP alpha-dT12and MP 5' alph...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.20.4551
更新日期:1998-10-15 00:00:00
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw559
更新日期:2016-10-14 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx584
更新日期:2017-09-06 00:00:00
abstract::Perturbation and time-course data sets, in combination with computational approaches, can be used to infer transcriptional regulatory networks which ultimately govern the developmental pathways and responses of cells. Here, we individually knocked down the four transcription factors PU.1, IRF8, MYB and SP1 in the huma...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq729
更新日期:2010-12-01 00:00:00