While human immunodeficiency virus 1(HIV-1) infectionis controlled through continuous, life-long use of a combination of drugs targeting different steps of the virus cycle, HIV-1 is never completely eradicated from th...While human immunodeficiency virus 1(HIV-1) infectionis controlled through continuous, life-long use of a combination of drugs targeting different steps of the virus cycle, HIV-1 is never completely eradicated from the body. Despite decades of research there is still no effective vaccine to prevent HIV-1 infection. Therefore, the possibility of an RNA interference(RNAi)-based cure has become an increasingly explored approach. Endogenous gene expression is controlled at both, transcriptional and post-transcriptional levels by noncoding RNAs, which act through diverse molecular mechanisms including RNAi. RNAi has the potential to control the turning on/off of specific genes through transcriptional gene silencing(TGS), as well as finetuning their expression through post-transcriptional gene silencing(PTGS). In this review we will describe in detail the canonical RNAi pathways for PTGS and TGS, the relationship of TGS with other silencing mechanisms and will discuss a variety of approaches developed to suppress HIV-1 via manipulation of RNAi. We will briefly compare RNAi strategies against other approaches developed to target the virus, highlighting their potential to overcome the major obstacle to finding a cure, which is the specific targeting of the HIV-1 reservoir within latently infected cells.展开更多
In plants, post-transcriptional gene silencing(PTGS) protects the genome from foreign genes and restricts the expression of certain endogenous genes for proper development. Here, we review the recent progress about ho...In plants, post-transcriptional gene silencing(PTGS) protects the genome from foreign genes and restricts the expression of certain endogenous genes for proper development. Here, we review the recent progress about how the unwanted PTGS is avoided in plants. As a decision-making step of PTGS, aberrant transcripts from most endogenous coding genes are strictly sorted to the bidirectional RNA decay pathways in cytoplasm but not to the short interference RNA(si RNA)-mediated PTGS, with the exception of a few development-relevant endogenous si RNA-producing genes. We also discuss a finely balanced PTGS threshold model that plants fully take advantage of the power of PTGS without self-harm.展开更多
Objective The aim of this review was to assess RNA interference (RNAi) and its possibility as a potential and powerful tool to develop highly specific double-stranded RNA ( dsRNA) or small interfering RNA (siRNA) base...Objective The aim of this review was to assess RNA interference (RNAi) and its possibility as a potential and powerful tool to develop highly specific double-stranded RNA ( dsRNA) or small interfering RNA (siRNA) based gene-silencing therapeutics. Data sources The data used in this review were obtained from the current RNAi-related research reports. Study selection dsRNA-mediated RNAi has recently emerged as a powerful reverse genetic tool to silence, gene expression in multiple organisms. The discovery that synthetic duplexes of 21 nucleotides siRNAs trigger gene-specific silencing in mammalian cells has further expanded the utility of RNAi in to the mammalian system. Data extraction The currently published papers reporting the discovery and mechanism of RNAi phenomena and application of RNAi on gene function in mammalian cells were included. Data synthesis Since the recent development of RNAi technology in the mammalian system, investigators have used RNAi to elucidate gene function, and to develop gene-based therapeutics by delivery exogenous siRNA or siRNA expressing vector. The general and sequence-specific inhibitory effects of RNAi that will be selective, long-term, and systemic to modulate gene targets mentioned in similar reports have caused much concern about its effectiveness in mammals and its eventual use as a therapeutic mordality. Conclusions It is certain that the ability of RNAi in mammals to silence specific genes, either when transfected directly as siRNAs or when generated from DNA vectors, will undoubtedly accelerate the study of gene function and might also be used as a potentially useful method to develop highly gene-specific therapeutic methods. It is also expected that RNAi might one day be used to treat human diseases.展开更多
Multicellular organisms, like higher plants, need to coordinate their growth and development and to cope with environmental cues. To achieve this, various signal molecules are transported between neighboring cells and...Multicellular organisms, like higher plants, need to coordinate their growth and development and to cope with environmental cues. To achieve this, various signal molecules are transported between neighboring cells and distant organs to control the fate of the recipient cells and organs. RNA silencing produces cell non-autonomous signal molecules that can move over short or long distances leading to the sequence specific silencing of a target gene in a well defined area of cells or throughout the entire plant,respectively. The nature of these signal molecules, the route of silencing spread, and the genes involved in their production, movement and reception are discussed in this review. Additionally, a short section on features of silencing spread in animal models is presented at the end of this review.展开更多
The invasive plant Mikania micrantha Kunth(M.micrantha)from South America poses a significant threat to the stability and biodiversity of ecosystems.However,an effective and economical method to control M.micrantha is...The invasive plant Mikania micrantha Kunth(M.micrantha)from South America poses a significant threat to the stability and biodiversity of ecosystems.However,an effective and economical method to control M.micrantha is still lacking.RNA interference(RNAi)has been widely studied and applied in agriculture for trait improvement.Spray-induced gene silencing(SIGS)can produce RNAi silencing effects without introducing heritable modifications to the plant genome and is becoming a novel nontransformation strategy for plant protection.In this study,the genes encoding chlorophyll a/b-binding proteins were selected as targets of RNAi,based on high-throughput sequencing of M.micrantha transcriptome and bioinformatic analyses of sequence specificity.Three types of RNAi molecules,double-stranded RNA,RNAi nanomicrosphere,and short hairpin RNA(shRNA),with their corresponding short interfering RNA sequences were designed and synthesized for SIGS vector construction,from which each RNAi molecule was transcribed and extracted to be sprayed on M.micrantha leaves.Whereas water-treated control leaves remained green,leaves treated with RNAi molecules turned yellow and eventually wilted.Quantitative real-time PCR showed that the expression levels of target genes were significantly reduced in the RNAi-treated groups compared with those of the control,suggesting that all three types of RNAi herbicides effectively silenced the endogenous target genes,which are essential for the growth of M.micrantha.We also found that shRNA showed better silencing efficiency than the other two molecules.Taken together,our study successfully designed three types of RNAi-based herbicides that specifically silenced endogenous target genes and controlled the growth of M.micrantha.Moreover,we identified a gene family encoding chlorophyll a/b-binding proteins that is important for the growth and development of M.micrantha and could serve as potential targets for controlling the spread of M.micrantha.展开更多
文摘While human immunodeficiency virus 1(HIV-1) infectionis controlled through continuous, life-long use of a combination of drugs targeting different steps of the virus cycle, HIV-1 is never completely eradicated from the body. Despite decades of research there is still no effective vaccine to prevent HIV-1 infection. Therefore, the possibility of an RNA interference(RNAi)-based cure has become an increasingly explored approach. Endogenous gene expression is controlled at both, transcriptional and post-transcriptional levels by noncoding RNAs, which act through diverse molecular mechanisms including RNAi. RNAi has the potential to control the turning on/off of specific genes through transcriptional gene silencing(TGS), as well as finetuning their expression through post-transcriptional gene silencing(PTGS). In this review we will describe in detail the canonical RNAi pathways for PTGS and TGS, the relationship of TGS with other silencing mechanisms and will discuss a variety of approaches developed to suppress HIV-1 via manipulation of RNAi. We will briefly compare RNAi strategies against other approaches developed to target the virus, highlighting their potential to overcome the major obstacle to finding a cure, which is the specific targeting of the HIV-1 reservoir within latently infected cells.
基金supported by the National Basic Research Program of China(2012CB910902)the National Natural Science Foundation of China(9121730591017010)to H.G
文摘In plants, post-transcriptional gene silencing(PTGS) protects the genome from foreign genes and restricts the expression of certain endogenous genes for proper development. Here, we review the recent progress about how the unwanted PTGS is avoided in plants. As a decision-making step of PTGS, aberrant transcripts from most endogenous coding genes are strictly sorted to the bidirectional RNA decay pathways in cytoplasm but not to the short interference RNA(si RNA)-mediated PTGS, with the exception of a few development-relevant endogenous si RNA-producing genes. We also discuss a finely balanced PTGS threshold model that plants fully take advantage of the power of PTGS without self-harm.
文摘Objective The aim of this review was to assess RNA interference (RNAi) and its possibility as a potential and powerful tool to develop highly specific double-stranded RNA ( dsRNA) or small interfering RNA (siRNA) based gene-silencing therapeutics. Data sources The data used in this review were obtained from the current RNAi-related research reports. Study selection dsRNA-mediated RNAi has recently emerged as a powerful reverse genetic tool to silence, gene expression in multiple organisms. The discovery that synthetic duplexes of 21 nucleotides siRNAs trigger gene-specific silencing in mammalian cells has further expanded the utility of RNAi in to the mammalian system. Data extraction The currently published papers reporting the discovery and mechanism of RNAi phenomena and application of RNAi on gene function in mammalian cells were included. Data synthesis Since the recent development of RNAi technology in the mammalian system, investigators have used RNAi to elucidate gene function, and to develop gene-based therapeutics by delivery exogenous siRNA or siRNA expressing vector. The general and sequence-specific inhibitory effects of RNAi that will be selective, long-term, and systemic to modulate gene targets mentioned in similar reports have caused much concern about its effectiveness in mammals and its eventual use as a therapeutic mordality. Conclusions It is certain that the ability of RNAi in mammals to silence specific genes, either when transfected directly as siRNAs or when generated from DNA vectors, will undoubtedly accelerate the study of gene function and might also be used as a potentially useful method to develop highly gene-specific therapeutic methods. It is also expected that RNAi might one day be used to treat human diseases.
基金co-financed by the European Union(European Social Fund–ESF)Greek national funds through the Operational Program"Education and Lifelong Learning"of the National Strategic Reference Framework(NSRF)–Research Funding Program:Heracleitus Ⅱ+1 种基金the European Social Fund(G.M.)Postdoctoral Grant LS1-1190(F.V)
文摘Multicellular organisms, like higher plants, need to coordinate their growth and development and to cope with environmental cues. To achieve this, various signal molecules are transported between neighboring cells and distant organs to control the fate of the recipient cells and organs. RNA silencing produces cell non-autonomous signal molecules that can move over short or long distances leading to the sequence specific silencing of a target gene in a well defined area of cells or throughout the entire plant,respectively. The nature of these signal molecules, the route of silencing spread, and the genes involved in their production, movement and reception are discussed in this review. Additionally, a short section on features of silencing spread in animal models is presented at the end of this review.
基金This research was financially supported by grants from the Shenzhen Science and Technology Program,China(Grant No.JCYJ20190808115005598)National Natural Science Foundation of China(Grant No.31801078)+1 种基金Guangdong Innovation Research Team Fun(Grant No.2014ZT05S078),Natural Science Foundation of SZU(Grant.No.2019080)the Undergraduate Academic Competition Project of Shenzhen University(Grant No.803-0000290846).
文摘The invasive plant Mikania micrantha Kunth(M.micrantha)from South America poses a significant threat to the stability and biodiversity of ecosystems.However,an effective and economical method to control M.micrantha is still lacking.RNA interference(RNAi)has been widely studied and applied in agriculture for trait improvement.Spray-induced gene silencing(SIGS)can produce RNAi silencing effects without introducing heritable modifications to the plant genome and is becoming a novel nontransformation strategy for plant protection.In this study,the genes encoding chlorophyll a/b-binding proteins were selected as targets of RNAi,based on high-throughput sequencing of M.micrantha transcriptome and bioinformatic analyses of sequence specificity.Three types of RNAi molecules,double-stranded RNA,RNAi nanomicrosphere,and short hairpin RNA(shRNA),with their corresponding short interfering RNA sequences were designed and synthesized for SIGS vector construction,from which each RNAi molecule was transcribed and extracted to be sprayed on M.micrantha leaves.Whereas water-treated control leaves remained green,leaves treated with RNAi molecules turned yellow and eventually wilted.Quantitative real-time PCR showed that the expression levels of target genes were significantly reduced in the RNAi-treated groups compared with those of the control,suggesting that all three types of RNAi herbicides effectively silenced the endogenous target genes,which are essential for the growth of M.micrantha.We also found that shRNA showed better silencing efficiency than the other two molecules.Taken together,our study successfully designed three types of RNAi-based herbicides that specifically silenced endogenous target genes and controlled the growth of M.micrantha.Moreover,we identified a gene family encoding chlorophyll a/b-binding proteins that is important for the growth and development of M.micrantha and could serve as potential targets for controlling the spread of M.micrantha.
