scholarly journals RNA Interference: Biology, Mechanism, and Applications

2003 ◽  
Vol 67 (4) ◽  
pp. 657-685 ◽  
Author(s):  
Neema Agrawal ◽  
P. V. N. Dasaradhi ◽  
Asif Mohmmed ◽  
Pawan Malhotra ◽  
Raj K. Bhatnagar ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Defense Mechanisms ◽  
Specific Gene ◽  
Small Interfering Rnas ◽  
Allelic Series ◽  
Rnase Iii ◽  
Heterochromatin Formation ◽  
Regulatory Processes ◽  
Micro Rnas ◽  
And Function

SUMMARY Double-stranded RNA-mediated interference (RNAi) is a simple and rapid method of silencing gene expression in a range of organisms. The silencing of a gene is a consequence of degradation of RNA into short RNAs that activate ribonucleases to target homologous mRNA. The resulting phenotypes either are identical to those of genetic null mutants or resemble an allelic series of mutants. Specific gene silencing has been shown to be related to two ancient processes, cosuppression in plants and quelling in fungi, and has also been associated with regulatory processes such as transposon silencing, antiviral defense mechanisms, gene regulation, and chromosomal modification. Extensive genetic and biochemical analysis revealed a two-step mechanism of RNAi-induced gene silencing. The first step involves degradation of dsRNA into small interfering RNAs (siRNAs), 21 to 25 nucleotides long, by an RNase III-like activity. In the second step, the siRNAs join an RNase complex, RISC (RNA-induced silencing complex), which acts on the cognate mRNA and degrades it. Several key components such as Dicer, RNA-dependent RNA polymerase, helicases, and dsRNA endonucleases have been identified in different organisms for their roles in RNAi. Some of these components also control the development of many organisms by processing many noncoding RNAs, called micro-RNAs. The biogenesis and function of micro-RNAs resemble RNAi activities to a large extent. Recent studies indicate that in the context of RNAi, the genome also undergoes alterations in the form of DNA methylation, heterochromatin formation, and programmed DNA elimination. As a result of these changes, the silencing effect of gene functions is exercised as tightly as possible. Because of its exquisite specificity and efficiency, RNAi is being considered as an important tool not only for functional genomics, but also for gene-specific therapeutic activities that target the mRNAs of disease-related genes.

scholarly journals Chromatin regulates expression of small RNAs to help maintain transposon methylome homeostasis in Arabidopsis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ranjith K. Papareddy ◽  
Katalin Páldi ◽  
Subramanian Paulraj ◽  
Ping Kao ◽  
Stefan Lutzmayer ◽  
...  
Keyword(s):  
Growth And Development ◽  
Germ Line ◽  
Small Interfering Rnas ◽  
Chromatin States ◽  
Heterochromatin Formation ◽  
Cellular Processes ◽  
A Cell ◽  
Decondensed Chromatin ◽  
And Function ◽  
New Generation

Abstract Background Eukaryotic genomes are partitioned into euchromatic and heterochromatic domains to regulate gene expression and other fundamental cellular processes. However, chromatin is dynamic during growth and development and must be properly re-established after its decondensation. Small interfering RNAs (siRNAs) promote heterochromatin formation, but little is known about how chromatin regulates siRNA expression. Results We demonstrate that thousands of transposable elements (TEs) produce exceptionally high levels of siRNAs in Arabidopsis thaliana embryos. TEs generate siRNAs throughout embryogenesis according to two distinct patterns depending on whether they are located in euchromatic or heterochromatic regions of the genome. siRNA precursors are transcribed in embryos, and siRNAs are required to direct the re-establishment of DNA methylation on TEs from which they are derived in the new generation. Decondensed chromatin also permits the production of 24-nt siRNAs from heterochromatic TEs during post-embryogenesis, and siRNA production from bipartite-classified TEs is controlled by their chromatin states. Conclusions Decondensation of heterochromatin in response to developmental, and perhaps environmental, cues promotes the transcription and function of siRNAs in plants. Our results indicate that chromatin-mediated siRNA transcription provides a cell-autonomous homeostatic control mechanism to help reconstitute pre-existing chromatin states during growth and development including those that ensure silencing of TEs in the future germ line.

scholarly journals T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer

2005 ◽  
Vol 201 (9) ◽  
pp. 1367-1373 ◽  
Author(s):  
Bradley S. Cobb ◽  
Tatyana B. Nesterova ◽  
Elizabeth Thompson ◽  
Arnulf Hertweck ◽  
Eric O'Connor ◽  
...  
Keyword(s):  
T Cell ◽  
Mammalian Cells ◽  
Early Stage ◽  
Early Embryo ◽  
Specific Gene ◽  
Small Interfering Rnas ◽  
Developmentally Regulated ◽  
Micro Rnas ◽  
Wide Range

The ribonuclease III enzyme Dicer is essential for the processing of micro-RNAs (miRNAs) and small interfering RNAs (siRNAs) from double-stranded RNA precursors. miRNAs and siRNAs regulate chromatin structure, gene transcription, mRNA stability, and translation in a wide range of organisms. To provide a model system to explore the role of Dicer-generated RNAs in the differentiation of mammalian cells in vivo, we have generated a conditional Dicer allele. Deletion of Dicer at an early stage of T cell development compromised the survival of αβ lineage cells, whereas the numbers of γδ-expressing thymocytes were not affected. In developing thymocytes, Dicer was not required for the maintenance of transcriptional silencing at pericentromeric satellite sequences (constitutive heterochromatin), the maintenance of DNA methylation and X chromosome inactivation in female cells (facultative heterochromatin), and the stable shutdown of a developmentally regulated gene (developmentally regulated gene silencing). Most remarkably, given that one third of mammalian mRNAs are putative miRNA targets, Dicer seems to be dispensable for CD4/8 lineage commitment, a process in which epigenetic regulation of lineage choice has been well documented. Thus, although Dicer seems to be critical for the development of the early embryo, it may have limited impact on the implementation of some lineage-specific gene expression programs.

scholarly journals Human Argonaute2 and Argonaute3 are catalytically activated by different lengths of guide RNA

2020 ◽  
Author(s):  
Mi Seul Park ◽  
GeunYoung Sim ◽  
Audrey C. Kehling ◽  
Kotaro Nakanishi
Keyword(s):  
Gene Silencing ◽  
Fold Increase ◽  
Specific Gene ◽  
Small Interfering Rnas ◽  
Guide Rna ◽  
Guide Rnas ◽  
Argonaute Proteins ◽  
Complementary Rnas ◽  
Standing Question

AbstractRNA interfering is a eukaryote-specific gene silencing by 20∼23 nucleotide (nt) microRNAs and small interfering RNAs that recruit Argonaute proteins to complementary RNAs for degradation. In humans, Argonaute2 (AGO2) has been known as the only slicer while Argonaute3 (AGO3) barely cleaves RNAs. Therefore, the intrinsic slicing activity of AGO3 remains controversial and a long-standing question. Here, we report 14-nt 3′ end-shortened variants of let-7a, miR-27a, and specific miR-17-92 families that make AGO3 an extremely competent slicer by an ∼ 82-fold increase in target cleavage. These RNAs, named cleavage-inducing tiny guide RNAs (cityRNAs), conversely lower the activity of AGO2, demonstrating that AGO2 and AGO3 have different optimum guide lengths for target cleavage. Our study sheds light on the role of tiny guide RNAs.

Specific gene silencing using small interfering RNAs in fish embryos

2003 ◽  
Vol 310 (4) ◽  
pp. 1089-1095 ◽  
Author(s):  
Surintorn Boonanuntanasarn ◽  
Goro Yoshizaki ◽  
Toshio Takeuchi
Keyword(s):  
Gene Silencing ◽  
Specific Gene ◽  
Small Interfering Rnas ◽  
Fish Embryos

scholarly journals An enhancer screen identifies new suppressors of small-RNA-mediated epigenetic gene silencing

PLoS Genetics ◽  
2021 ◽  
Vol 17 (6) ◽  
pp. e1009645
Author(s):  
Yukiko Shimada ◽  
Sarah H. Carl ◽  
Merle Skribbe ◽  
Valentin Flury ◽  
Tahsin Kuzdere ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Small Rna ◽  
De Novo ◽  
Single Amino Acid ◽  
Small Interfering Rnas ◽  
Nascent Transcript ◽  
Protein Coding ◽  
Heterochromatin Formation ◽  
Transcript Processing ◽  
Epigenetic Gene Silencing

Small non-protein coding RNAs are involved in pathways that control the genome at the level of chromatin. In Schizosaccharomyces pombe, small interfering RNAs (siRNAs) are required for the faithful propagation of heterochromatin that is found at peri-centromeric repeats. In contrast to repetitive DNA, protein-coding genes are refractory to siRNA-mediated heterochromatin formation, unless siRNAs are expressed in mutant cells. Here we report the identification of 20 novel mutant alleles that enable de novo formation of heterochromatin at a euchromatic protein-coding gene by using trans-acting siRNAs as triggers. For example, a single amino acid substitution in the pre-mRNA cleavage factor Yth1 enables siRNAs to trigger silent chromatin formation with unparalleled efficiency. Our results are consistent with a kinetic nascent transcript processing model for the inhibition of small-RNA-directed de novo formation of heterochromatin and lay a foundation for further mechanistic dissection of cellular activities that counteract epigenetic gene silencing.

scholarly journals Human Argonaute2 and Argonaute3 are catalytically activated by different lengths of guide RNA

2020 ◽  
Vol 117 (46) ◽  
pp. 28576-28578
Author(s):  
Mi Seul Park ◽  
GeunYoung Sim ◽  
Audrey C. Kehling ◽  
Kotaro Nakanishi
Keyword(s):  
Gene Silencing ◽  
Specific Gene ◽  
Small Interfering Rnas ◽  
Guide Rna ◽  
Guide Rnas ◽  
Argonaute Proteins ◽  
Rna Interfering ◽  
Complementary Rnas ◽  
Standing Question

RNA interfering is a eukaryote-specific gene silencing by 20∼23-nucleotide (nt) microRNAs and small interfering RNAs that recruit Argonaute proteins to complementary RNAs for degradation. In humans, Argonaute2 (AGO2) has been known as the only slicer while Argonaute3 (AGO3) barely cleaves RNAs. Therefore, the intrinsic slicing activity of AGO3 remains controversial and a long-standing question. Here, we report 14-nt 3′ end-shortened variants of let-7a, miR-27a, and specific miR-17–92 families that make AGO3 an extremely competent slicer, increasing target cleavage up to ∼82-fold in some instances. These RNAs, named cleavage-inducing tiny guide RNAs (cityRNAs), conversely lower the activity of AGO2, demonstrating that AGO2 and AGO3 have different optimum guide lengths for target cleavage. Our study sheds light on the role of tiny guide RNAs.

scholarly journals Chemical strategies for strand selection in short-interfering RNAs

RSC Advances ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 2415-2426
Author(s):  
Andrew J. Varley ◽  
Jean-Paul Desaulniers
Keyword(s):  
Rna Interference ◽  
Gene Silencing ◽  
Rnai Pathway ◽  
Specific Gene ◽  
Small Interfering Rnas ◽  
Chemical Strategies

Therapeutic small interfering RNAs (siRNAs) are double stranded RNAs capable of potent and specific gene silencing through activation of the RNA interference (RNAi) pathway.

The role of non-coding RNAs

2019 ◽  
pp. 69-79
Author(s):  
John C. Lucchesi
Keyword(s):  
Target Genes ◽  
Centromeric Heterochromatin ◽  
Small Interfering Rnas ◽  
Protein Coding ◽  
Heterochromatin Formation ◽  
Short Rnas ◽  
Micro Rnas ◽  
Rrna Maturation ◽  
Non Coding Rnas

Most of the genome is transcribed into non-coding transcripts that far exceed in number the transcripts of protein-coding genes. These RNAs are subdivided into different classes. Long non-coding RNAs (lncRNAs) are at least 200 nucleotides in length and are transcribed from promoter, coding, intergenic or enhancer regions (eRNAs). These RNAs repress or enhance the transcription of target genes by facilitating the interaction between promoters and enhancers or by interacting with transcription factors and targeting histone-modifying enzymes. Short non-coding RNAs include a diverse group of functional types: miRNAs (micro RNAs) and siRNAs (small interfering RNAs) are negative regulators of gene expression; piRNAs (Piwi-interacting RNAs) suppress the action of transposable elements in the germline; snRNAs (small nuclear RNAs) are involved in mRNA splicing and rRNA maturation; tRNA-derived non-coding RNAs are involved in the cellular reaction to stress and in the repression of gene function. Additional short RNAs are rasiRNAs (repeat-associated small interfering RNAs) that appear to be involved in centromeric heterochromatin formation.

scholarly journals Chromatin Regulates Bipartite-Classified Small RNA Expression to Maintain Epigenome Homeostasis in Arabidopsis

2020 ◽  
Author(s):  
Ranjith K. Papareddy ◽  
Katalin Páldi ◽  
Subramanian Paulraj ◽  
Ping Kao ◽  
Michael D. Nodine
Keyword(s):  
Growth And Development ◽  
Germ Line ◽  
Small Interfering Rnas ◽  
Chromatin States ◽  
Heterochromatin Formation ◽  
Cellular Processes ◽  
A Cell ◽  
Decondensed Chromatin ◽  
And Function ◽  
New Generation

AbstractEukaryotic genomes are partitioned into euchromatic and heterochromatic domains to regulate gene expression and other fundamental cellular processes. However, chromatin is dynamic during growth and development, and must be properly re-established after its decondensation. Small interfering RNAs (siRNAs) promote heterochromatin formation in eukaryotes, but little is known about how chromatin regulates siRNA transcription. We demonstrated that thousands of transposable elements (TEs) produce exceptionally high levels of siRNAs in Arabidopsis thaliana embryos. Depending on whether they are located in euchromatic or heterochromatic regions of the genome, bipartite-classified TEs generate siRNAs throughout embryogenesis according to two distinct patterns. siRNAs are transcribed in embryos and required to direct the re-establishment of DNA methylation on TEs from which they are derived in the new generation. Decondensed chromatin also permits the production of 24-nt siRNAs from heterochromatic TEs during post-embryogenesis, and siRNA production from bipartite-classified TEs is controlled by their chromatin states. Decondensation of heterochromatin in response to developmental, and perhaps environmental, cues promotes the transcription and function of siRNAs in plants. Our results indicate that chromatin-mediated siRNA transcription provides a cell-autonomous homeostatic control mechanism to reconstitute pre-existing chromatin states during growth and development including those that ensure silencing of TEs in the future germ line.

scholarly journals Dicer Functions in Aquatic Species

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Yasuko Kitagishi ◽  
Naoko Okumura ◽  
Hitomi Yoshida ◽  
Chika Tateishi ◽  
Yuri Nishimura ◽  
...  
Keyword(s):  
Recent Progress ◽  
Defense Mechanism ◽  
Aquatic Species ◽  
Small Interfering Rnas ◽  
Rnase Iii ◽  
Catalytic Subunits ◽  
Double Stranded Rna ◽  
Related Research ◽  
Micro Rnas ◽  
Endogenous Genes

Dicer is an RNase III enzyme with two catalytic subunits, which catalyzes the cleavage of double-stranded RNA to small interfering RNAs and micro-RNAs, which are mainly involved in invasive nucleic acid defense and endogenous genes regulation. Dicer is abundantly expressed in embryos, indicating the importance of the protein in early embryonic development. In addition, Dicer is thought to be involved in defense mechanism against foreign nucleic acids such as viruses. This paper will mainly focus on the recent progress of Dicer-related research and discuss potential RNA interference pathways in aquatic species.

Sign in / Sign up

Export Citation Format

Share Document