scholarly journals Specificity Principles in RNA-Guided Targeting

2016 ◽  
Author(s):  
Namita Bisaria ◽  
Inga Jarmoskaite ◽  
Daniel Herschlag
Keyword(s):  
Gene Regulation ◽  
Rna Interference ◽  
Binding Affinity ◽  
Small Rna ◽  
Kinetic Models ◽  
Specific Gene ◽  
Rational Engineering ◽  
Target Rna ◽  
Target Activity ◽  
Derived Rules

ABSTRACTRNA-guided nucleases (RGNs) provide sequence-specific gene regulation through base-pairing interactions between a small RNA guide and target RNA or DNA. RGN systems, which include CRISPR-Cas9 and RNA interference (RNAi), hold tremendous promise as programmable tools for engineering and therapeutic purposes. However, pervasive targeting of sequences that closely resemble the intended target has remained a major challenge, limiting the reliability and interpretation of RGN activity and the range of possible applications. Efforts to reduce off-target activity and enhance RGN specificity have led to a collection of empirically derived rules, which often paradoxically include decreased binding affinity of the RNA-guided nuclease to its target. Here we demonstrate that simple kinetic considerations of the targeting reaction can explain these and other literature observations. The kinetic models described provide a foundation for understanding RGN systems and a necessary physical and functional framework for their rational engineering.

scholarly journals RNA Interference in Fungi: Pathways, Functions, and Applications

2011 ◽  
Vol 10 (9) ◽  
pp. 1148-1155 ◽  
Author(s):  
Yunkun Dang ◽  
Qiuying Yang ◽  
Zhihong Xue ◽  
Yi Liu
Keyword(s):  
Gene Regulation ◽  
Rna Interference ◽  
Small Rna ◽  
Rnai Machinery ◽  
Content Type ◽  
Heterochromatin Formation ◽  
Rna Molecules ◽  
Cellular Processes ◽  
Rna Biogenesis ◽  
Core Components

ABSTRACT Small RNA molecules of about 20 to 30 nucleotides function in gene regulation and genomic defense via conserved eukaryotic RNA interference (RNAi)-related pathways. The RNAi machinery consists of three core components: Dicer, Argonaute, and RNA-dependent RNA polymerase. In fungi, the RNAi-related pathways have three major functions: genomic defense, heterochromatin formation, and gene regulation. Studies of Schizosaccharomyces pombe and Neurospora , and other fungi have uncovered surprisingly diverse small RNA biogenesis pathways, suggesting that fungi utilize RNAi-related pathways in various cellular processes to adapt to different environmental conditions. These studies also provided important insights into how RNAi functions in eukaryotic systems in general. In this review, we will discuss our current understanding of the fungal RNAi-related pathways and their functions, with a focus on filamentous fungi. We will also discuss how RNAi can be used as a tool in fungal research.

SiMiSnoRNA: Collection of siRNA, miRNA, and snoRNA database for RNA interference / SiMiSnoRNA: RNA Interferansı için siRNA, miRNA ve snoRNA veritabanında depolanan siRNA, miRNA, and snoRNA koleksiyonları

2015 ◽  
Vol 40 (6) ◽  
Author(s):  
Umesh Kalathiya ◽  
Monikaben Padariya ◽  
Maciej Baginski ◽  
Chintankumar Padariya
Keyword(s):  
Gene Expression ◽  
Rna Interference ◽  
Small Rna ◽  
Regulation Of Gene Expression ◽  
Specific Gene ◽  
Sequence Information ◽  
Rna Molecules ◽  
Inhibit Gene Expression ◽  
Considerable Impact ◽  
Interfering Rna

AbstractObjective: The discovery of sequence specific gene silencing which occurs due to the presence of double- stranded RNAs has considerable impact on biology, revealing an unknown level of regulation of gene expression. This process is known as RNA interference (RNAi) or RNA silencing in which RNA molecules inhibit gene expression, typically by causing the destruction of specific mRNA molecule. Two types of small RNA molecules-small interfering RNA (siRNA) and microRNA (miRNA) are central to RNA interference. Therefore, SMethods: SResults: A flexible web-based search engine is developed to obtain fast access to specific small RNA sequence information.Conclusion: BLAST search analysis within S

scholarly journals A unique histone 3 lysine 14 chromatin signature underlies tissue-specific gene regulation

2021 ◽  
Author(s):  
Isabel Regadas ◽  
Olle Dahlberg ◽  
Roshan Vaid ◽  
Oanh Ho ◽  
Sergey Belikov ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Specific Gene ◽  
Chromatin Signature ◽  
Tissue Specific ◽  
Tissue Specific Gene ◽  
Histone 3

scholarly journals Androgen and glucocorticoid receptor direct distinct transcriptional programs by receptor-specific and shared DNA binding sites

2021 ◽  
Vol 49 (7) ◽  
pp. 3856-3875
Author(s):  
Marina Kulik ◽  
Melissa Bothe ◽  
Gözde Kibar ◽  
Alisa Fuchs ◽  
Stefanie Schöne ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Transcription Factor ◽  
Dna Binding ◽  
Receptor Binding ◽  
Binding Sites ◽  
Specific Gene ◽  
Functional Diversification ◽  
Enhancer Activity ◽  
Sequence Composition

Abstract The glucocorticoid (GR) and androgen (AR) receptors execute unique functions in vivo, yet have nearly identical DNA binding specificities. To identify mechanisms that facilitate functional diversification among these transcription factor paralogs, we studied them in an equivalent cellular context. Analysis of chromatin and sequence suggest that divergent binding, and corresponding gene regulation, are driven by different abilities of AR and GR to interact with relatively inaccessible chromatin. Divergent genomic binding patterns can also be the result of subtle differences in DNA binding preference between AR and GR. Furthermore, the sequence composition of large regions (>10 kb) surrounding selectively occupied binding sites differs significantly, indicating a role for the sequence environment in guiding AR and GR to distinct binding sites. The comparison of binding sites that are shared shows that the specificity paradox can also be resolved by differences in the events that occur downstream of receptor binding. Specifically, shared binding sites display receptor-specific enhancer activity, cofactor recruitment and changes in histone modifications. Genomic deletion of shared binding sites demonstrates their contribution to directing receptor-specific gene regulation. Together, these data suggest that differences in genomic occupancy as well as divergence in the events that occur downstream of receptor binding direct functional diversification among transcription factor paralogs.

scholarly journals Regulation and imaging of gene expression via an RNA interference antagonistic biomimetic probe

2017 ◽  
Vol 8 (7) ◽  
pp. 4973-4977 ◽  
Author(s):  
Kai Zhang ◽  
Xue-Jiao Yang ◽  
Wei Zhao ◽  
Ming-Chen Xu ◽  
Jing-Juan Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Rna Interference ◽  
Living Cells

A versatile strategy is reported which permits gene regulation and imaging in living cells via an RNA interference antagonistic probe.

Dynamic landscape of immune cell-specific gene regulation in immune-mediated diseases

Cell ◽  
2021 ◽  
Author(s):  
Mineto Ota ◽  
Yasuo Nagafuchi ◽  
Hiroaki Hatano ◽  
Kazuyoshi Ishigaki ◽  
Chikashi Terao ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Immune Cell ◽  
Specific Gene ◽  
Immune Mediated ◽  
Dynamic Landscape

Pursuing gene regulation 'logic' via RNA interference and chromatin immunoprecipitation

2006 ◽  
Vol 7 (7) ◽  
pp. 692-697 ◽  
Author(s):  
Caiyi C Li ◽  
Vladimir R Ramirez-Carrozzi ◽  
Stephen T Smale
Keyword(s):  
Gene Regulation ◽  
Rna Interference ◽  
Chromatin Immunoprecipitation

Advances in Specific Gene Knockdown of Therapeutic Targets by RNA Interference

2018 ◽  
Vol 24 (23) ◽  
pp. 2631-2631
Author(s):  
Fabiola Garcia Praça ◽  
Maria Vitória Lopes Badra Bentley
Keyword(s):  
Rna Interference ◽  
Therapeutic Targets ◽  
Gene Knockdown ◽  
Specific Gene

scholarly journals Identification of MEF2-regulated genes during muscle differentiation

2004 ◽  
Vol 20 (1) ◽  
pp. 143-151 ◽  
Author(s):  
James Paris ◽  
Carl Virtanen ◽  
Zhibin Lu ◽  
Mark Takahashi
Keyword(s):  
Gene Regulation ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Neuromuscular Junctions ◽  
Muscle Differentiation ◽  
Signaling Cascades ◽  
Specific Gene ◽  
Genetic Mechanisms ◽  
Selection Parameters ◽  
First Time

Although a great deal has been elucidated concerning the mechanisms regulating muscle differentiation, little is known about transcription factor-specific gene regulation. Our understanding of the genetic mechanisms regulating cell differentiation is quite limited. Much of what has been defined centers on regulatory signaling cascades and transcription factors. Surprisingly few studies have investigated the association of genes with specific transcription factors. To address these issues, we have utilized a method coupling chromatin immunoprecipitation and CpG microarrays to characterize the genes associated with MEF2 in differentiating C2C12 cells. Results demonstrated a defined binding pattern over the course of differentiation. Filtered data demonstrated 9 clones to be elevated at 0 h, 792 at 6 h, 163 by 1 day, and 316 at 3 days. Using unbiased selection parameters, we selected a subset of 291 prospective candidates. Clones were sequenced and filtered for removal of redundancy between clones and for the presence of repetitive elements. We were able to place 50 of these on the mouse genome, and 20 were found to be located near well-annotated genes. From this list, previously undefined associations with MEF2 were discovered. Many of these genes represent proteins involved in neurogenesis, neuromuscular junctions, signaling and metabolism. The remaining clones include many full-length cDNA and represent novel gene targets. The results of this study provides for the first time, a unique look at gene regulation at the level of transcription factor binding in differentiating muscle.

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