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分子遗传学阅读文献:基因表达调控之三

已有 9806 次阅读 2008-9-3 14:35 |个人分类:科学感想|系统分类:科研笔记| 基因, 分子遗传学阅读文献, 表达调控

The silence of genes

 

Hunter P. The silence of genes. Is genomic imprinting the software of evolution or just a battleground for gender conflict? EMBO Rep. 2007 May; 8 (5): 441-3.

The silence of genes

 

Return to the RNAi world: rethinking gene expression and evolution

 

Mello CC. Return to the RNAi world: rethinking gene expression and evolution. Cell Death Differ. 2007 Dec; 14 (12): 2013-20.

 

Thanks to the Nobel Foundation for permission to publish this Lecture. Here we report the transcript of the lecture delivered by Professor Craig C Mello at the Nobel Prize ceremony. Professor Mello vividly describes the years of research that led to the discovery of RNA interference and the molecular mechanisms that regulate this fundamental cellular process. The turning point of discoveries and the role played by all his colleagues and collaborators are described, making this a wonderful report of the adventure of research. The lecture explains in simple language the importance of this discovery that has added a great level of complexity to the way cells regulate protein levels; moreover, it points out the beauty and importance of Caenorhabditis elegans as a model organism and how the use of this model has greatly contributed to the advance of science. Finally, Professor Mello leaves us with a number of questions that his research has raised and that will require years of future research to be answered.

 

 Return to the RNAi world-rethinking gene expression and evolution

 

RNAi: a defensive RNA-silencing against viruses and transposable elements

 

Buchon N, Vaury C. RNAi: a defensive RNA-silencing against viruses and transposable elements. Heredity. 2006 Feb; 96 (2): 195-202.

 

RNA silencing is a form of nucleic-acid-based immunity, targeting viruses and genomic repeated sequences. First documented in plants and invertebrate animals, this host defence has recently been identified in mammals. RNAi is viewed as a conserved ancient mechanism protecting genomes from nucleic acid invaders. However, these tamed sequences are known to occasionally escape this host surveillance and invade the genome of their host. This response is consistent with the overall idea that parasitic sequences compete with cells to systematically counter host defences. Using examples taken from the current literature, we illustrate the dynamic move-countermove game played between these two protagonists, the host cell and its parasitic sequences, and discuss the consequences of this game on genome stability.

 

 RNAi-a defensive RNA-silencing against viruses and transposable elements

 

Chromatin-based silenceing mechanism

 

Bender J. Chromatin-based silencing mechanisms. Curr Opin Plant Biol. 2004 Oct; 7 (5): 521-6.

 

Eukaryotic genomes are organized into regions of transcriptionally active euchromatin and transcriptionally inactive heterochromatin. In plant genomes, heterochromatin is marked by methylation of cytosine and methylation of histone H3 at lysine 9. Heterochromatin formation is targeted to transposons as a means of defending the host genome against the deleterious effects of these sequences. Heterochromatin is directed to transposon sequences by transposon-derived aberrant RNA species and functions to prevent unwanted transcription and movement. Formation of heterochromatin at rRNA-encoding genes and centromere-associated repeats might also involve an RNA-based mechanism that is designed to stabilize these potentially labile structures.

 Chromatin-based silenceing mechanism

 

Role of histone and DNA methylation in gene regulation

 

Vaillant I, Paszkowski J. Role of histone and DNA methylation in gene regulation. Curr Opin Plant Biol. 2007 Oct; 10 (5): 528-33. Epub 2007 Aug 9.

 

Transcription is known to be regulated by given chromatin states, distinguished as transcriptionally active euchromatin and silent heterochromatin. In plants, silencing in heterochromatin is associated with hypermethylation of DNA and specific covalent modifications of histone H3. Several lines of evidence have suggested that maintenance of DNA methylation patterns at CG sequences is responsible for the formation of stable and thus heritable activity states termed epialleles. By contrast, histone modification and DNA methylation outside CGs confer the flexibility of transcriptional regulation necessary for plant development and adaptive responses to the environment. Recent studies have refined our understanding of the biological significance of and the molecular mechanisms involved in the interplay between DNA and histone H3 methylation.

 Role of histone and DNA methylation in gene regulation

 

DNA-RNA-protein gang together in silence

 

Stokes T. DNA-RNA-protein gang together in silence. Trends Plant Sci. 2003 Feb; 8 (2): 53-5.

 

Two recent reports demonstrate interdependence between DNA and histone methylation in Arabidopsis. ddm1 (decrease in DNA methylation 1) mutants switch histone methylation from a form associated with inactive chromatin to a form connected to actively transcribed genomic regions. The loss of DNA methylation and shift in histone methylation cause transcriptional derepression of heterochromatic regions. In a related report, small RNAs in Schizosaccharomyces pombe mark histone methylation to form heterochromatin, suggesting that methylation systems work alongside RNA metabolism.

 DNA-RNA-protein gang together in silence

 

RNA interference against viruses: strike and counterstrike

 

Haasnoot J, Westerhout EM, Berkhout B. RNA interference against viruses: strike and counterstrike. Nat Biotechnol. 2007 Dec; 25 (12): 1435-43.

 

RNA interference (RNAi) is a conserved sequence-specific, gene-silencing mechanism that is induced by double-stranded RNA. RNAi holds great promise as a novel nucleic acid-based therapeutic against a wide variety of diseases, including cancer, infectious diseases and genetic disorders. Antiviral RNAi strategies have received much attention and several compounds are currently being tested in clinical trials. Although induced RNAi is able to trigger profound and specific inhibition of virus replication, it is becoming clear that RNAi therapeutics are not as straightforward as we had initially hoped. Difficulties concerning toxicity and delivery to the right cells that earlier hampered the development of antisense-based therapeutics may also apply to RNAi. In addition, there are indications that viruses have evolved ways to escape from RNAi. Proper consideration of all of these issues will be necessary in the design of RNAi-based therapeutics for successful clinical intervention of human pathogenic viruses.

 RNA interference against viruses-strike and counterstrike

 

RNA silencing and antiviral defence in plants

 

Wang MB, Metzlaff M. RNA silencing and antiviral defense in plants. Curr Opin Plant Biol. 2005 Apr; 8 (2): 216-22.

 

Much progress has been made recently in identifying the molecular components of RNA silencing in plants, and in understanding their roles in the biogenesis of small interfering RNAs and microRNAs, in RNA-directed DNA methylation, and in RNA-mediated antiviral defense. However, many crucial questions remain unanswered. What are the molecular bases of sense and antisense transgene-mediated silencing? Why does silencing only appear to spread through transgenes? Plant viruses encode silencing suppressors to counteract host RNA silencing, and some of these suppressors affect microRNA accumulation and function and hence normal plant development. Is viral pathogenicity determined, partly or entirely, by their silencing suppressor activity?

 RNA silencing and antiviral defence in plants

 

RNA silencing bridging the gaps in wheat extracts

 

Voinnet O. RNA silencing bridging the gaps in wheat extracts. Trends Plant Sci. 2003 Jul; 8 (7): 307-9.

 

In plants, RNA silencing plays important roles in antiviral defence, genome integrity and development. This process involves nucleotide sequence-specific interactions that are mediated by small RNA molecules of 21-25 nucleotides. Although the core biochemical reactions of RNA silencing have been well characterized in animals, such information was crucially missing in plants. Recent work now addresses this question and reveals an overall similarity between the plant and animal RNA-silencing pathways, as well as some intriguing plant-specific aspects.

  

RNA silencing bridging the gaps in wheat extracts

 

RNA silencing in plants-defense and counterdefense

 

Vance V, Vaucheret H. RNA silencing in plants--defense and counterdefense. Science. 2001 Jun 22; 292 (5525): 2277-80.

 

RNA silencing is a remarkable type of gene regulation based on sequence-specific targeting and degradation of RNA. The term encompasses related pathways found in a broad range of eukaryotic organisms, including fungi, plants, and animals. In plants, it serves as an antiviral defense, and many plant viruses encode suppressors of silencing. The emerging view is that RNA silencing is part of a sophisticated network of interconnected pathways for cellular defense, RNA surveillance, and development and that it may become a powerful tool to manipulate gene expression experimentally.

 RNA silencing in plants-defense and counterdefense

 

Strategies for silencing human disease using RNA interference

 

Kim DH, Rossi JJ. Strategies for silencing human disease using RNA interference. Nat Rev Genet. 2007 Mar; 8 (3): 173-84.

 

Since the first description of RNA interference (RNAi) in animals less than a decade ago, there has been rapid progress towards its use as a therapeutic modality against human diseases. Advances in our understanding of the mechanisms of RNAi and studies of RNAi in vivo indicate that RNAi-based therapies might soon provide a powerful new arsenal against pathogens and diseases for which treatment options are currently limited. Recent findings have highlighted both promise and challenges in using RNAi for therapeutic applications. Design and delivery strategies for RNAi effector molecules must be carefully considered to address safety concerns and to ensure effective, successful treatment of human diseases.

 Strategies for silencing human disease using RNA interference

 

Role of short RNAs in gene silencing

 

Waterhouse PM, Wang MB, Finnegan EJ. Role of short RNAs in gene silencing. Trends Plant Sci. 2001 Jul; 6 (7): 297-301.

 

Recent research has revealed the existence of an elegant defence mechanism in plants and lower eukaryotes. The mechanism, known in plants as post-transcriptional gene silencing, works through sequence-specific degradation of RNA. It appears to be directed by double-stranded RNA, associated with the production of short 21-25 nt RNAs, and spread through the plant by a diffusible signal. The short RNAs are implicated as the guides for both a nuclease complex that degrades the mRNA and a methyltransferase complex that methylates the DNA of silenced genes. It has also been suggested that these short RNAs might be the mobile silencing signal, a suggestion that has been challenged recently.

 

Role of short RNAs in gene silencing



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