A brief history of RNAi: the silence of the genes

Sen, George L.; Blau, Helen M.

doi:10.1096/fj.06-6014rev

Cited by 190 publications

(123 citation statements)

References 60 publications

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“…This is consistent with predictions by others (as reviewed in ref. 41) that the holoRISC is a multiunit complex. In this context it is also noteworthy that native agarose gel-electrophoresis experiments showed that longer (Ͼ100 nt) TBSV ss-and dsRNAs are associated with the high-MW fractions displaying ribonuclease activity (data not shown), indicating that these may be components of the in vivo assembled antiviral holocomplex.…”

Section: Tbsv-preferential Ribonuclease Is Associated With a Discretementioning

confidence: 99%

RNAi-associated ssRNA-specific ribonucleases in Tombusvirus P19 mutant-infected plants and evidence for a discrete siRNA-containing effector complex

Omarov

Ciomperlik

Scholthof

2007

Proc. Natl. Acad. Sci. U.S.A.

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Tomato bushy stunt virus (TBSV) and other tombusviruses encode a p19 protein (P19), which is a suppressor of RNAi. Wild-type TBSV or p19-defective mutants initially show a similar infection course in Nicotiana benthamiana, but the absence of an active P19 results in viral RNA degradation followed by recovery from infection. P19 homodimers sequester 21-nt virus-derived duplex siRNAs, and it is thought that this prevents the programming of an antiviral RNAinduced silencing complex to avoid viral RNA degradation. Here we report on chromatographic fractionation (gel filtration, ion exchange, and hydroxyapatite) of extracts from healthy or infected Nicotiana benthamiana plants in combination with in vitro assays for ribonuclease activity and detection of TBSV-derived siRNAs. Only extracts of plants infected with p19 mutants provided a source of sequence-nonspecific but ssRNA-targeted in vitro ribonuclease activity that coeluted with components of a wide molecular weight range. In addition, we isolated a discrete Ϸ500-kDa protein complex that contained Ϸ21-nt TBSV-derived siRNAs and that exhibited ribonuclease activity that was TBSV sequencepreferential, ssRNA-specific, divalent cation-dependent, and insensitive to a ribonuclease inhibitor. We believe that this study provides biochemical evidence for a virus-host system that infection in the absence of a fully active RNAi suppressor induces ssRNA-specific ribonuclease activity, including that conferred by a RNA-induced silencing complex, which is likely the cause for the recovery of plants from infection.suppression ͉ silencing ͉ RNA-induced silencing complex

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Section: Tbsv-preferential Ribonuclease Is Associated With a Discretementioning

confidence: 99%

RNAi-associated ssRNA-specific ribonucleases in Tombusvirus P19 mutant-infected plants and evidence for a discrete siRNA-containing effector complex

Omarov

Ciomperlik

Scholthof

2007

Proc. Natl. Acad. Sci. U.S.A.

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“…The RNAi phenomenon was first reported by Napoli and Jorgensen in 1990 [59]. They found a surprising observation in petunias while trying to deepen the purple color of these flowers.…”

Section: Introductionmentioning

confidence: 89%

“…They introduced a pigment-producing gene under the control of a powerful promoter and observed white color instead of deep purple. Jorgensen named the observed phenomenon "cosuppression", since the expression of both the introduced gene and the homologous endogenous gene was suppressed [53,59]. The suppression of the endogenous gene by the introduction of homologous RNA sequence was first noticed by Romano and Macino in Neurospora crassa in 1992 [58,59].…”

Section: Introductionmentioning

confidence: 99%

“…Jorgensen named the observed phenomenon "cosuppression", since the expression of both the introduced gene and the homologous endogenous gene was suppressed [53,59]. The suppression of the endogenous gene by the introduction of homologous RNA sequence was first noticed by Romano and Macino in Neurospora crassa in 1992 [58,59]. In animals, the first evidence that dsRNA could lead to gene silencing came from work in Caenorhabditis elegans [30].…”

Section: Introductionmentioning

confidence: 99%

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RNA interference and its therapeutic potential

2011

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AbstractRNA interference is a technique that has become popular in the past few years. This is a biological method to detect the activity of a specific gene within a cell. RNAi is the introduction of homologous double stranded RNA to specifically target a gene’s product resulting in null or hypomorphic phenotypes. This technique involves the degradation of specific mRNA by using small interfering RNA. Both microRNA (miRNA) and small interfering RNA (siRNA) are directly related to RNA interference. RNAi mechanism is being explored as a new technique for suppressing gene expression. It is an important issue in the treatment of various diseases. This review considers different aspects of RNAi technique including its history of discovery, molecular mechanism, gene expression study, advantages of this technique against previously used techniques, barrier associated with this technique, and its therapeutic application.

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“…The establishment of stable silencing was originally thought to be a post-transcriptional process, however, multiple lines of evidence from different organisms suggest that small RNAs also promote silencing in the nucleus at the transcriptional level. It has been shown that small RNAs guide chromatin remodeling proteins to specific DNA sequences by binding to nascent RNA transcripts, leading to cytosine methylation (in plants, fission yeast, and even in mice [8,77]) and deposition of histone modifications (in plants, fission yeast, worms, and flies [78,79]). The interaction between small RNAs and chromatin remodeling factors is reciprocal.…”

Section: Mechanisms That Enable Long-lasting Rnaimentioning

confidence: 99%

Guest list or black list: heritable small RNAs as immunogenic memories

Rechavi

2014

Trends in Cell Biology

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Small RNA-mediated gene silencing plays a pivotal role in genome immunity by recognizing and eliminating viruses and transposons which otherwise may colonize the genome. However, this can be challenging since individual genomic parasites are highly diverse, and employ multiple immune evasion techniques. In this review, I discuss a new theory proposing that the integrity of the germline is maintained by transgenerationally-transmitted RNA "memories" that record ancestral gene expression patterns, and delineate "Self" from "Foreign" sequences. To maintain such recollection two tactics are employed in parallel: "black listing" of invading nucleic acids, and "guest listing" of endogenous genes. Studies in a number of organisms have shown that this memorization is used by the next generation small RNAs to act as "Inherited Vaccines" that ambush invading elements, or as "Inherited Licenses" that grant the transcription of autogenous sequences. KeywordsSmall RNA; Transgenerational Inheritance; Inherited Immunity; Self Vs. Non-Self; "Inherited Vaccines" Overview of transgenerational inheritanceEvolution progresses through an interplay between two major forces, selection and variation. Since the formulation of the Modern Synthesis the theory holds that the environment is limited in its contribution to the evolutionary course of action -it affects selection, but not the degree of variation [1,2]. However, recent discoveries in epigenetics suggest that the environment may influence variability as well [1]. If the parental environment is predictive of the conditions that the progeny will face (often for sessile or short-lived organisms), epigenetic responses can change the output of the encoded genetic information in an adaptive manner [3]. For example, the water flea Daphnia changes its normal developmental course and develops a "helmet" that protects it from predators, if it is born to a mother that survived a similar attack [4].Correspondence to: odedrechavi@gmail.com. Over the years, controversy surrounded the study of environmentally affected transgenerational inheritance. Today, an improved understanding of epigenetic mechanisms at the molecular level has provided a logical background to explain how, heretically, an adaptive acquired trait could become heritable [5]. Several epigenetic mechanisms could regulate the expression of relevant genes during transgenerational inheritance including DNA methylation, histone modification, and transmission of regulatory RNAs. Moreover, in many organisms, these pathways appear to be interconnected [5][6][7][8]. Europe PMC Funders GroupThis review will concentrate on recent discoveries that establish a role for small RNAs in transgenerational transmission of acquired defense. Furthermore, exciting examples of RNA-mediated non-Mendelian genetic effects will be discussed, along with their possible implications for the study of evolution and immunology. RNA-mediated gene silencing and inheritanceSince the original discovery that small RNAs derived from exogenously-provided dou...

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A brief history of RNAi: the silence of the genes

Cited by 190 publications

References 60 publications

RNAi-associated ssRNA-specific ribonucleases in Tombusvirus P19 mutant-infected plants and evidence for a discrete siRNA-containing effector complex

RNAi-associated ssRNA-specific ribonucleases in Tombusvirus P19 mutant-infected plants and evidence for a discrete siRNA-containing effector complex

RNA interference and its therapeutic potential

Guest list or black list: heritable small RNAs as immunogenic memories

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