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FEBS Lett,
2005]
RNA interference (RNAi) is a form of gene silencing induced by double stranded RNA (dsRNA) that is processed into short interfering RNAs (siRNAs). RNAi can induce both post-transcriptional and transcriptional gene silencing. In Caenorhabditis elegans, there are several distinct pathways where post-transcriptional or/and transcriptional RNAi mechanisms are involved. RNAi in C. elegans is also systemic and heritable. This review will discuss RNAi related pathways, features of RNAi in C. elegans and possibilities of endogenous gene regulation by RNAi.
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J Bioenerg Biomembr,
2007]
RNAi is an evolutionarily conserved gene-silencing phenomenon that can be triggered by exogenous delivery of double stranded RNA to organisms. In Caenorhabditis elegans, the response to dsRNA is remarkably robust, and systemic RNAi responses are often observed. We have taken a genetic approach using this organism to better understand the mechanisms that facilitate RNAi. By analyzing strains of RNAi-defective mutants, we have uncovered an unexpected role for ABC transporters in RNAi and related silencing mechanisms. Ten of the sixty ABC transporter genes encoded in the C. elegans genome are required for robust RNAi. We will present data that highlights common features of these genes relative to their roles in RNAi, including genetic interactions with other components of the RNAi machinery. We will also describe unique roles for some transporter genes in endogenous RNAi-related processes.
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Parasitology,
2012]
RNA interference (RNAi) is a powerful research tool that has enabled molecular insights into gene activity, pathway analysis, partial loss-of-function phenotypes, and large-scale genomic discovery of gene function. While RNAi works extremely well in the non-parasitic nematode C. elegans, it is also especially useful in organisms that lack facile genetic analysis. Extensive genetic analysis of the mechanisms, delivery and regulation of RNAi in C. elegans has provided mechanistic and phenomenological insights into why RNAi is so effective in this species. These insights are useful for the testing and development of RNAi in other nematodes, including parasitic nematodes where more effective RNAi would be extremely useful. Here, we review the current advances in C. elegans for RNA delivery methods, regulation of cell autonomous and systemic RNAi phenomena, and implications of enhanced RNAi mutants. These discussions, with a focus on mechanism and cross-species application, provide new perspectives for optimizing RNAi in other species.
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Differentiation,
2004]
The phenomenon of RNA-mediated interference (RNAi) was first discovered in the nematode Caenorhabditis elegans, in which introduction of double-stranded RNA causes specific inactivation of genes with corresponding sequences. Technical advances in RNAi methodology and the availability of the complete genome sequence have enabled the high-throughput, genome-wide RNAi analysis of this organism. Several groups have used large-scale RNAi to systematically examine every C. elegans gene for knock-down phenotypes, providing basal information to be mined in more detailed studies. Now, in addition to functional genomic RNAi analyses, high-throughput RNAi is also routinely used for rapid, genome-wide screens for genes involved in specific biological processes. The integration of high-throughput RNAi experiments with other large-scale data, such as DNA microarrays and protein-protein interaction maps, enhances the speed and reliability of such screens. The accumulation of RNAi phenotype data dramatically accelerates our understanding of this organism
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Adv Genet,
2002]
RNA interference in Caenorhabditis elegans is a type of homology dependent posttranscriptional gene silencing induced by dsRNA. In this chapter we describe the history of the discovery of RNAi, its systemic nature, inheritance, and connection to other homology-dependent silencing phenomena like co-suppression and transcriptional gene silencing. We discuss RNAi-deficient mutants in C. elegans as well as characterized components of the RNAi, pathway, the molecular mechanism of RNAi, and its possible role in development and immunity.
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Dev Biol,
2001]
RNA-mediated genetic interference (RNAi) has become a very useful tool for analyzing gene function in development and other processes. RNAi can be used as a complement to traditional genetic studies or as a primary means of determining biological function. However, the efficacy of RNAi depends on a variety of factors that the researcher must take into consideration. This review focuses on germline development in the nematode, Caenorhabditis elegans, and discusses the uses and limitations of RNAi in providing new information about gene function as well as the possible endogenous role RNAi plays in germline physiology.
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Wiley Interdiscip Rev RNA,
2011]
RNA interference (RNAi) leads to sequence-specific knockdown of gene function. The approach can be used in large-scale screens to interrogate function in various model organisms and an increasing number of other species. Genome-scale RNAi screens are routinely performed in cultured or primary cells or in vivo in organisms such as C. elegans. High-throughput RNAi screening is benefitting from the development of sophisticated new instrumentation and software tools for collecting and analyzing data, including high-content image data. The results of large-scale RNAi screens have already proved useful, leading to new understandings of gene function relevant to topics such as infection, cancer, obesity, and aging. Nevertheless, important caveats apply and should be taken into consideration when developing or interpreting RNAi screens. Some level of false discovery is inherent to high-throughput approaches and specific to RNAi screens, false discovery due to off-target effects (OTEs) of RNAi reagents remains a problem. The need to improve our ability to use RNAi to elucidate gene function at large scale and in additional systems continues to be addressed through improved RNAi library design, development of innovative computational and analysis tools and other approaches.
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Semin Cell Dev Biol,
2021]
RNA interference (RNAi) is a highly conserved gene regulatory phenomenon whereby Argonaute/small RNA (AGO/sRNA) complexes target transcripts by antisense complementarity to modulate gene expression. While initially appreciated as a cytoplasmic process, RNAi can also occur in the nucleus where AGO/sRNA complexes are recruited to nascent transcripts. Nuclear AGO/sRNA complexes recruit co-factors that regulate transcription by inhibiting RNA Polymerase II, modifying histones, compacting chromatin and, in some organisms, methylating DNA. C. elegans has a longstanding history in unveiling the mechanisms of RNAi and has become an outstanding model to delineate the mechanisms underlying nuclear RNAi. In this review we highlight recent discoveries in the field of nuclear RNAi in C. elegans and the roles of nuclear RNAi in the regulation of gene expression, chromatin organization, genome stability, and transgenerational epigenetic inheritance.
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Brief Funct Genomic Proteomic,
2008]
The RNA interference (RNAi) method for targeted gene silencing is widely used in Caenorhabditis elegans for large-scale functional genomic studies, analysis of limited gene sets and detailed analysis of individual gene function. The application of RNAi has identified genes that participate in various aspects of development, physiology and cell biology. In addition, RNAi has been used to identify interacting genes and to study functionally redundant genes. This review discusses the various applications of RNAi in C. elegans, focusing particularly on the analysis of developmental processes.
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Nat Cell Biol,
2000]
In many species, introduction of double-stranded RNA (dsRNA) induces potent and specific gene silencing, a phenomenon called RNA interference or RNAi. The apparently widespread nature of RNAi in eukaryotes, ranging from trypanosome to mouse, has sparked great interest from both applied and fundamental standpoints. Here we review the technical improvements being made to increase the experimental potential of this technique. We also discuss recent advances in uncovering the proteins that act during the RNAi process, discoveries that have revealed enticing links between transposition, transgene silencing and RNAi.