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Science China. Life Sciences Mar 2016In plants, post-transcriptional gene silencing (PTGS) protects the genome from foreign genes and restricts the expression of certain endogenous genes for proper... (Review)
Review
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 (siRNA)-mediated PTGS, with the exception of a few development-relevant endogenous siRNA-producing genes. We also discuss a finely balanced PTGS threshold model that plants fully take advantage of the power of PTGS without self-harm.
Topics: Cytoplasm; Gene Expression Regulation, Plant; Gene Silencing; Plants; RNA Interference; RNA Stability; RNA, Plant; RNA, Small Interfering
PubMed: 26718356
DOI: 10.1007/s11427-015-4972-7 -
Methods in Molecular Biology (Clifton,... 2019Plant microRNAs are an endogenous class of small regulatory RNA central to the posttranscriptional regulation of gene expression in plant development and environmental... (Review)
Review
Plant microRNAs are an endogenous class of small regulatory RNA central to the posttranscriptional regulation of gene expression in plant development and environmental stress adaptation or in response to pathogen challenge. The plant microRNA pathway is readily separated into two distinct stages: (1) the production stage, which is localized to the plant cell nucleus and where the microRNA small RNA is processed from a double-stranded RNA precursor transcript, and (2) the action stage, which is localized to the plant cell cytoplasm and where the mature microRNA small RNA is loaded into an effector complex and is used by the complex as a sequence specificity guide to direct expression repression of target genes harboring highly complementary microRNA target sequences. Historical research indicated that the plant microRNA pathway was a highly structured, almost linear pathway requiring a small set of core machinery proteins. However, contemporary research has demonstrated that the plant microRNA pathway is highly dynamic, and to allow for this flexibility, a large and highly functionally diverse set of machinery proteins is now known to be required. For example, recent research has shown that plant microRNAs can regulate target gene expression via a translational repression mechanism of RNA silencing in addition to the standard messenger RNA cleavage-based mechanism of RNA silencing: a mode of RNA silencing originally assigned to all plant microRNAs. Using Arabidopsis thaliana as our model system, here we report on both the core and auxiliary sets of machinery proteins now known to be required for both microRNA production and microRNA action in plants.
Topics: Animals; Arabidopsis; Gene Expression Regulation, Plant; MicroRNAs; RNA Interference; RNA, Messenger; RNA, Plant
PubMed: 30701489
DOI: 10.1007/978-1-4939-9042-9_2 -
Plant, Cell & Environment Sep 2023RNA interference (RNAi) technology is a promising and effective approach for pest insect management. Owing to its sequence-guided working mechanism, RNAi has a high... (Review)
Review
RNA interference (RNAi) technology is a promising and effective approach for pest insect management. Owing to its sequence-guided working mechanism, RNAi has a high degree of species-selectivity, thus minimizing potential adverse effects on nontarget organisms. Recently, engineering plastid (chloroplast) genome, rather than the nuclear genome, to produce double-stranded RNAs has emerged as a powerful way to protect plants from multiple arthropod pests. Here, we review the recent progresses in the plastid-mediated RNAi (PM-RNAi) approach for pest control and the factors influencing its efficacy, and propose the strategies for further efficiency improvement. We also discuss the current challenges and the biosafety-related issues of PM-RNAi technology that need to be addressed for commercial production.
Topics: Animals; RNA Interference; Pest Control; Insecta; Plastids; RNA, Double-Stranded
PubMed: 37332196
DOI: 10.1111/pce.14652 -
Progress in Molecular Biology and... 2024RNA therapies involve the utilization of natural and artificial RNA molecules to control the expression and function of cellular genes and proteins. Initializing from... (Review)
Review
RNA therapies involve the utilization of natural and artificial RNA molecules to control the expression and function of cellular genes and proteins. Initializing from 1990s, RNA therapies now show the rapid growth in the development and application of RNA therapeutics for treating various conditions, especially for undruggable diseases. The outstanding success of recent mRNA vaccines against COVID-19 infection again highlighted the important role of RNA therapies in future medicine. In this review, we will first briefly provide the crucial investigations on RNA therapy, from the first pieces of discovery on RNA molecules to clinical applications of RNA therapeutics. We will then classify the mechanisms of RNA therapeutics from various classes in the treatment of diseases. To emphasize the huge potential of RNA therapies, we also provide the key RNA products that have been on clinical trials or already FDA-approved. With comprehensive knowledge on RNA biology, and the advances in analysis, technology and computer-aid science, RNA therapies can bring a promise to be more expanding to the market in the future.
Topics: Humans; RNA; COVID-19 Vaccines; RNA Interference
PubMed: 38360006
DOI: 10.1016/bs.pmbts.2023.12.012 -
International Journal of Molecular... Aug 2023is a pathogenic fungus of that is epidemic in the Qinling Mountains. However, an effective gene interference strategy is needed to characterize the pathogenic genes in...
is a pathogenic fungus of that is epidemic in the Qinling Mountains. However, an effective gene interference strategy is needed to characterize the pathogenic genes in this fungus on a functional level. Using the RNA silencing vector pSilent-1 as a template, we established an RNA interference genetic transformation system mediated by GV3101, which is suitable for the gene study for by homologous recombination and strain interference system screening. The LqFlbA gene was silenced using the RNA interference approach described above, and the resulting transformants displayed various levels of silencing with a gene silencing effectiveness ranging from 41.8% to 91.4%. The LqFlbA-RNAi mutant displayed altered colony morphology, sluggish mycelium growth, and diminished pathogenicity toward the host in comparison to the wild type. The results indicate that this method provides a useful reverse genetic system for studying the gene function of , and that plays a crucial role in the growth, development, and pathogenicity of .
Topics: RNA Interference; Gene Silencing; Agrobacterium tumefaciens; Epidemics; Transformation, Genetic
PubMed: 37629189
DOI: 10.3390/ijms241613009 -
British Journal of Pharmacology Apr 2021RNAi effectors (e.g. siRNA, shRNA and miRNA) can trigger the silencing of specific genes causing alteration of genomic functions becoming a new therapeutic area for the... (Review)
Review
RNAi effectors (e.g. siRNA, shRNA and miRNA) can trigger the silencing of specific genes causing alteration of genomic functions becoming a new therapeutic area for the treatment of infectious diseases, neurodegenerative disorders and cancer. In cancer treatment, RNAi effectors showed potential immunomodulatory actions by down-regulating immuno-suppressive proteins, such as PD-1 and CTLA-4, which restrict immune cell function and present challenges in cancer immunotherapy. Therefore, compared with extracellular targeting by antibodies, RNAi-mediated cell-intrinsic disruption of inhibitory pathways in immune cells could promote an increased anti-tumour immune response. Along with non-viral vectors, DNA-based RNAi strategies might be a more promising method for immunomodulation to silence multiple inhibitory pathways in T cells than immune checkpoint blockade antibodies. Thus, in this review, we discuss diverse RNAi implementation strategies, with recent viral and non-viral mediated RNAi synergism to immunotherapy that augments the anti-tumour immunity. Finally, we provide the current progress of RNAi in clinical pipeline.
Topics: Humans; Immunotherapy; MicroRNAs; Neoplasms; RNA Interference; RNA, Small Interfering
PubMed: 33608889
DOI: 10.1111/bph.15414 -
Plant Physiology and Biochemistry : PPB Jan 2023Over the last two decades, significant advances have been made using genetic engineering technology to modify genes from various exotic origins and introduce them into... (Review)
Review
Over the last two decades, significant advances have been made using genetic engineering technology to modify genes from various exotic origins and introduce them into plants to induce favorable traits. RNA interference (RNAi) was discovered earlier as a natural process for controlling the expression of genes across all higher species. It aims to enhance precision and accuracy in pest/pathogen resistance, quality improvement, and manipulating the architecture of plants. However, it existed as a widely used technique recently. RNAi technologies could well be used to down-regulate any genes' expression without disrupting the expression of other genes. The use of RNA interference to silence genes in various organisms has become the preferred method for studying gene functions. The establishment of new approaches and applications for enhancing desirable characters is essential in crops by gene suppression and the refinement of knowledge of endogenous RNAi mechanisms in plants. RNAi technology in recent years has become an important and choicest method for controlling insects, pests, pathogens, and abiotic stresses like drought, salinity, and temperature. Although there are certain drawbacks in efficiency of this technology such as gene candidate selection, stability of trigger molecule, choice of target species and crops. Nevertheless, from past decade several target genes has been identified in numerous crops for their improvement towards biotic and abiotic stresses. The current review is aimed to emphasize the research done on crops under biotic and abiotic stress using RNAi technology. The review also highlights the gene regulatory pathways/gene silencing, RNA interference, RNAi knockdown, RNAi induced biotic and abiotic resistance and advancements in the understanding of RNAi technology and the functionality of various components of the RNAi machinery in crops for their improvement.
Topics: RNA Interference; Crops, Agricultural; Stress, Physiological; Gene Silencing
PubMed: 36529010
DOI: 10.1016/j.plaphy.2022.11.035 -
Cold Spring Harbor Symposia on... 2016Rapid and affordable tumor profiling has led to an explosion of genomic data that is facilitating the development of new cancer therapies. The potential of therapeutic... (Review)
Review
Rapid and affordable tumor profiling has led to an explosion of genomic data that is facilitating the development of new cancer therapies. The potential of therapeutic strategies aimed at inactivating the oncogenic lesions that contribute to the aberrant survival and proliferation of tumor cells has yielded remarkable success in some malignancies such as BRAF-mutant melanoma and BCR-ABL expressing chronic myeloid leukemia. However, the direct inhibition of several well-established oncoproteins in some of these cancers is not possible or produces only transient benefits. Functional genomics represents a powerful approach for the identification of vulnerabilities linked to specific genetic alterations and has provided substantial insights into cancer signaling networks. Still, as inhibition of gene function can have diverse effects on both tumor and normal tissues, information on the potency of target inhibition on tumor growth as well as the toxic side effects of target inhibition are also needed. Here, we discuss our RNA interference (RNAi) pipeline for cancer target discovery based on our optimized short-hairpin RNA (shRNA) tools for negative selection screens and inducible RNAi platform that, in combination with embryonic stem cell (ESC)-based genetically engineered mouse models (GEMMs), enable deep in vivo target validation.
Topics: Animals; Cell Proliferation; Disease Models, Animal; Embryonic Stem Cells; Humans; RNA Interference; RNA, Small Interfering; Signal Transduction
PubMed: 28057848
DOI: 10.1101/sqb.2016.81.031096 -
International Journal of Molecular... Oct 2021Alternative RNA splicing is an important regulatory process used by genes to increase their diversity. This process is mainly executed by specific classes of RNA binding... (Review)
Review
Alternative RNA splicing is an important regulatory process used by genes to increase their diversity. This process is mainly executed by specific classes of RNA binding proteins that act in a dosage-dependent manner to include or exclude selected exons in the final transcripts. While these processes are tightly regulated in cells and tissues, little is known on how the dosage of these factors is achieved and maintained. Several recent studies have suggested that alternative RNA splicing may be in part modulated by microRNAs (miRNAs), which are short, non-coding RNAs (~22 nt in length) that inhibit translation of specific mRNA transcripts. As evidenced in tissues and in diseases, such as cancer and neurological disorders, the dysregulation of miRNA pathways disrupts downstream alternative RNA splicing events by altering the dosage of splicing factors involved in RNA splicing. This attractive model suggests that miRNAs can not only influence the dosage of gene expression at the post-transcriptional level but also indirectly interfere in pre-mRNA splicing at the co-transcriptional level. The purpose of this review is to compile and analyze recent studies on miRNAs modulating alternative RNA splicing factors, and how these events contribute to transcript rearrangements in tissue development and disease.
Topics: Alternative Splicing; Animals; Gene Expression; Humans; MicroRNAs; RNA Interference; Transcription, Genetic
PubMed: 34769047
DOI: 10.3390/ijms222111618 -
Expert Opinion on Drug Delivery 2023Among conventional and novel therapeutic approaches, the siRNA strategy stands out for treating disease by silencing the gene responsible for the corresponding disorder.... (Review)
Review
INTRODUCTION
Among conventional and novel therapeutic approaches, the siRNA strategy stands out for treating disease by silencing the gene responsible for the corresponding disorder. Gene silencing is supposedly intended to target any disease-causing gene, and therefore, several attempts and investments were made to exploit siRNA gene therapy and advance it into clinical settings. Despite the remarkable beneficial prospects, the applicability of siRNA therapeutics is very challenging due to various pathophysiological barriers that hamper its target reach, which is the cytosol, and execution of gene silencing action.
AREAS COVERED
The present review provides insights into the field of siRNA therapeutics, significant in vivo hurdles that mitigate the target accessibility of siRNA, and remedies to overcome these siRNA delivery challenges. Nonetheless, the current review also highlights the on-going clinical trials and the regulatory aspects of siRNA modalities.
EXPERT OPINION
The siRNAs have the potential to reach previously untreated target sites and silence the concerned gene owing to their modification as polymeric or lipidic nanoparticles, conjugates, and the application of advanced drug delivery strategies. With such mounting research attempts to improve the delivery of siRNA to target tissue, we might shortly witness revolutionary therapeutic outcomes, new approvals, and clinical implications.
Topics: RNA, Small Interfering; Gene Silencing; Genetic Therapy; Drug Delivery Systems; RNA Interference
PubMed: 37642354
DOI: 10.1080/17425247.2023.2251890