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Source: Nucleic Acids Research
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Total 88 results found since Jan 2013.
Programmable folding of fusion RNA in vivo and in vitro driven by pRNA 3WJ motif of phi29 DNA packaging motor
Misfolding and associated loss of function are common problems in constructing fusion RNA complexes due to changes in energy landscape and the nearest-neighbor principle. Here we report the incorporation and application of the pRNA-3WJ motif of the phi29 DNA packaging motor into fusion RNA with controllable and predictable folding. The motif included three discontinuous ~18 nucleotide (nt) fragments, displayed a distinct low folding energy (Shu D et al., Nature Nanotechnology, 2011, 6:658–667), and folded spontaneously into a leading core that enabled the correct folding of other functionalities fused to the RNA comp...
Source: Nucleic Acids Research - January 26, 2014 Category: Research Authors: Shu, D., Khisamutdinov, E. F., Zhang, L., Guo, P. Tags: RNA characterisation and manipulation Methods Online Source Type: research
siRNA enhances DNA-mediated interferon lambda-1 response through crosstalk between RIG-I and IFI16 signalling pathway
In addition to silencing specific genes, small interfering RNA (siRNA) transfection is also associated with the non-specific induction of inflammatory cytokines and type I interferon. Those so-called "off-target" effects have considerable implications for the interpretation of in vitro studies and clinical application of siRNA. The present study attempted to develop a better understanding of the mechanism involved in these off target effects. Synthesized siRNA significantly enhances DNA-mediated interferon lambda-1 response (IFN-1/IL-29), a newly characterized antiviral interferon in non-immune or primary immune cells. Thi...
Source: Nucleic Acids Research - December 28, 2013 Category: Research Authors: Sui, H., Zhou, M., Chen, Q., Lane, H. C., Imamichi, T. Tags: RNA Source Type: research
Independent parallel functions of p19 plant viral suppressor of RNA silencing required for effective suppressor activity
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 suppressor function, small interfering RNA (siRNA) binding, to investigate the biological role of VSR-mediated miR168 induction. Infection with the mutant virus carrying p19-3M VSR resulted in suppressed recovery phenotype despite the presence of free virus specific siRNAs. Analysis of the infected plants rev...
Source: Nucleic Acids Research - December 28, 2013 Category: Research Authors: Varallyay, E., Olah, E., Havelda, Z. Tags: RNA Source Type: research
E2F2 and CREB cooperatively regulate transcriptional activity of cell cycle genes
E2F2 is essential for the maintenance of T lymphocyte quiescence. To identify the full set of E2F2 target genes, and to gain further understanding of the role of E2F2 in transcriptional regulation, we have performed ChIP-chip analyses across the genome of lymph node–derived T lymphocytes. Here we show that during quiescence, E2F2 binds the promoters of a large number of genes involved in DNA metabolism and cell cycle regulation, concomitant with their transcriptional silencing. A comparison of ChIP-chip data with expression profiling data on resting E2f2–/– T lymphocytes identified a subset of 51 E2F2-spe...
Source: Nucleic Acids Research - December 5, 2013 Category: Research Authors: Laresgoiti, U., Apraiz, A., Olea, M., Mitxelena, J., Osinalde, N., Rodriguez, J. A., Fullaondo, A., Zubiaga, A. M. Tags: Gene Regulation, Chromatin and Epigenetics Source Type: research
DHX9 helicase is involved in preventing genomic instability induced by alternatively structured DNA in human cells
Sequences that have the capacity to adopt alternative (i.e. non-B) DNA structures in the human genome have been implicated in stimulating genomic instability. Previously, we found that a naturally occurring intra-molecular triplex (H-DNA) caused genetic instability in mammals largely in the form of DNA double-strand breaks. Thus, it is of interest to determine the mechanism(s) involved in processing H-DNA. Recently, we demonstrated that human DHX9 helicase preferentially unwinds inter-molecular triplex DNA in vitro. Herein, we used a mutation-reporter system containing H-DNA to examine the relevance of DHX9 activity on nat...
Source: Nucleic Acids Research - December 5, 2013 Category: Research Authors: Jain, A., Bacolla, A., del Mundo, I. M., Zhao, J., Wang, G., Vasquez, K. M. Tags: Genome Integrity, Repair and Replication Source Type: research
Optochemical control of RNA interference in mammalian cells
Short interfering RNAs (siRNAs) and microRNAs (miRNAs) have been widely used in mammalian tissue culture and model organisms to selectively silence genes of interest. One limitation of this technology is the lack of precise external control over the gene-silencing event. The use of photocleavable protecting groups installed on nucleobases is a promising strategy to circumvent this limitation, providing high spatial and temporal control over siRNA or miRNA activation. Here, we have designed, synthesized and site-specifically incorporated new photocaged guanosine and uridine RNA phosphoramidites into short RNA duplexes. We d...
Source: Nucleic Acids Research - December 5, 2013 Category: Research Authors: Govan, J. M., Young, D. D., Lusic, H., Liu, Q., Lively, M. O., Deiters, A. Tags: RNA Source Type: research
Increasing the complexity of chromatin: functionally distinct roles for replication-dependent histone H2A isoforms in cell proliferation and carcinogenesis
Replication-dependent histones are encoded by multigene families found in several large clusters in the human genome and are thought to be functionally redundant. However, the abundance of specific replication-dependent isoforms of histone H2A is altered in patients with chronic lymphocytic leukemia. Similar changes in the abundance of H2A isoforms are also associated with the proliferation and tumorigenicity of bladder cancer cells. To determine whether these H2A isoforms can perform distinct functions, expression of several H2A isoforms was reduced by siRNA knockdown. Reduced expression of the HIST1H2AC locus leads to in...
Source: Nucleic Acids Research - October 31, 2013 Category: Research Authors: Singh, R., Mortazavi, A., Telu, K. H., Nagarajan, P., Lucas, D. M., Thomas-Ahner, J. M., Clinton, S. K., Byrd, J. C., Freitas, M. A., Parthun, M. R. Tags: Gene Regulation, Chromatin and Epigenetics Source Type: research
ss-siRNAs allele selectively inhibit ataxin-3 expression: multiple mechanisms for an alternative gene silencing strategy
Single-stranded silencing RNAs (ss-siRNAs) provide an alternative approach to gene silencing. ss-siRNAs combine the simplicity and favorable biodistribution of antisense oligonucleotides with robust silencing through RNA interference (RNAi). Previous studies reported potent and allele-selective inhibition of human huntingtin expression by ss-siRNAs that target the expanded CAG repeats within the mutant allele. Mutant ataxin-3, the genetic cause of Machado–Joseph Disease, also contains an expanded CAG repeat. We demonstrate here that ss-siRNAs are allele-selective inhibitors of ataxin-3 expression and then redesign ss...
Source: Nucleic Acids Research - October 31, 2013 Category: Research Authors: Liu, J., Yu, D., Aiba, Y., Pendergraff, H., Swayze, E. E., Lima, W. F., Hu, J., Prakash, T. P., Corey, D. R. Tags: Synthetic Biology and Chemistry Source Type: research
Systems biology of Ewing sarcoma: a network model of EWS-FLI1 effect on proliferation and apoptosis
In this study, a network linking EWS-FLI1 to cell cycle and apoptosis phenotypes was constructed through an original method of network reconstruction. Transcriptome time-series after EWS-FLI1 silencing were used to identify core modulated genes by an original scoring method based on fitting expression profile dynamics curves. Literature data mining was then used to connect these modulated genes into a network. The validity of a subpart of this network was assessed by siRNA/RT-QPCR experiments on four additional Ewing cell lines and confirmed most of the links. Based on the network and the transcriptome data, CUL1 was ident...
Source: Nucleic Acids Research - October 18, 2013 Category: Research Authors: Stoll, G., Surdez, D., Tirode, F., Laud, K., Barillot, E., Zinovyev, A., Delattre, O. Tags: Computational Biology Source Type: research
Automated and assisted RNA resonance assignment using NMR chemical shift statistics
The three-dimensional structure determination of RNAs by NMR spectroscopy relies on chemical shift assignment, which still constitutes a bottleneck. In order to develop more efficient assignment strategies, we analysed relationships between sequence and 1H and 13C chemical shifts. Statistics of resonances from regularly Watson–Crick base-paired RNA revealed highly characteristic chemical shift clusters. We developed two approaches using these statistics for chemical shift assignment of double-stranded RNA (dsRNA): a manual approach that yields starting points for resonance assignment and simplifies decision trees and...
Source: Nucleic Acids Research - October 6, 2013 Category: Research Authors: Aeschbacher, T., Schmidt, E., Blatter, M., Maris, C., Duss, O., Allain, F. H.- T., Guntert, P., Schubert, M. Tags: Nucleic acid structure, RNA characterisation and manipulation Methods Online Source Type: research
Dicodon monitoring of protein synthesis (DiCoMPS) reveals levels of synthesis of a viral protein in single cells
In this study, we used cells infected with the Epizootic Hemorrhagic Disease Virus 2-Ibaraki and measured, through DiCoMPS, the synthesis of the viral non-structural protein 3 (NS3), which is enriched in the AUA:AUA dicodon. fl-tRNAIleUAU-generated FRET signals were specifically enhanced in infected cells, increased in the course of infection and were diminished on siRNA-mediated knockdown of NS3. Our results establish an experimental approach for the single-cell measurement of the levels of synthesis of a specific viral protein.
Source: Nucleic Acids Research - October 6, 2013 Category: Research Authors: Barhoom, S., Farrell, I., Shai, B., Dahary, D., Cooperman, B. S., Smilansky, Z., Elroy-Stein, O., Ehrlich, M. Tags: Ribosomes and Protein Translation Methods Online Source Type: research
The PRP6-like splicing factor STA1 is involved in RNA-directed DNA methylation by facilitating the production of Pol V-dependent scaffold RNAs
DNA methylation is a conserved epigenetic marker in plants and animals. In Arabidopsis, DNA methylation can be established through an RNA-directed DNA methylation (RdDM) pathway. By screening for suppressors of ros1, we identified STA1, a PRP6-like splicing factor, as a new RdDM regulator. Whole-genome bisulfite sequencing suggested that STA1 and the RdDM pathway share a large number of common targets in the Arabidopsis genome. Small RNA deep sequencing demonstrated that STA1 is predominantly involved in the accumulation of the siRNAs that depend on both Pol IV and Pol V. Moreover, the sta1 mutation partially reduces the l...
Source: Nucleic Acids Research - October 6, 2013 Category: Research Authors: Dou, K., Huang, C.-F., Ma, Z.-Y., Zhang, C.-J., Zhou, J.-X., Huang, H.-W., Cai, T., Tang, K., Zhu, J.-K., He, X.-J. Tags: Gene Regulation, Chromatin and Epigenetics Source Type: research
Differential roles of human Dicer-binding proteins TRBP and PACT in small RNA processing
During RNA interference and related gene regulatory pathways, the endonuclease Dicer cleaves precursor RNA molecules to produce microRNAs (miRNAs) and short interfering RNAs (siRNAs). Human cells encode a single Dicer enzyme that can associate with two different double-stranded RNA (dsRNA)-binding proteins, protein activator of PKR (PACT) and trans-activation response RNA-binding protein (TRBP). However, the functional redundancy or differentiation of PACT and TRBP in miRNA and siRNA biogenesis is not well understood. Using a reconstituted system, we show here that PACT and TRBP have distinct effects on Dicer-mediated dsRN...
Source: Nucleic Acids Research - July 15, 2013 Category: Research Authors: Lee, H. Y., Zhou, K., Smith, A. M., Noland, C. L., Doudna, J. A. Tags: Molecular Biology Source Type: research
The 26S proteasome drives trinucleotide repeat expansions
This study reports that the multi-functional protein Sem1 is a novel driver of TNR expansions in budding yeast. Mutants of SEM1 suppress up to 90% of expansions. Subsequent analysis showed that Sem1 facilitates expansions via its function in the 26S proteasome, a highly conserved multi-subunit complex with both proteolytic and non-proteolytic functions. The proteolytic function of the 26S proteasome is relevant to expansions, as mutation of additional proteasome components or treatment of yeast with a proteasome inhibitor suppressed CTG•CAG expansions. The 26S proteasome also drives expansions in human cells. In a hum...
Source: Nucleic Acids Research - June 26, 2013 Category: Research Authors: Concannon, C., Lahue, R. S. Tags: Genome Integrity, Repair and Replication Source Type: research
Molecular basis for improved gene silencing by Dicer substrate interfering RNA compared with other siRNA variants
The canonical exogenous trigger of RNA interference (RNAi) in mammals is small interfering RNA (siRNA). One promising application of RNAi is siRNA-based therapeutics, and therefore the optimization of siRNA efficacy is an important consideration. To reduce unfavorable properties of canonical 21mer siRNAs, structural and chemical variations to canonical siRNA have been reported. Several of these siRNA variants demonstrate increased potency in downstream readout-based assays, but the molecular mechanism underlying the increased potency is not clear. Here, we tested the performance of canonical siRNAs and several sequence-mat...
Source: Nucleic Acids Research - June 26, 2013 Category: Research Authors: Snead, N. M., Wu, X., Li, A., Cui, Q., Sakurai, K., Burnett, J. C., Rossi, J. J. Tags: RNA Source Type: research
