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Neuron Mar 2007RNA interference (RNAi), a mediator of gene silencing, has swiftly become one of the most exciting and applicable biological discoveries. There has been rapid progress... (Review)
Review
RNA interference (RNAi), a mediator of gene silencing, has swiftly become one of the most exciting and applicable biological discoveries. There has been rapid progress in identifying RNAi pathway components and elucidating the mechanisms of microRNA (miRNA) biogenesis and gene suppression. As a result, RNAi technologies have been successfully employed in a variety of systems as biological tools, and studies are underway to test the therapeutic utility of RNAi. In the span of several years, significant advances in the delivery of inhibitory RNAs in the nervous system have been made. We have glimpses into how endogenous miRNAs interface with neuronal development and function; in addition, RNAi has shown therapeutic efficacy in several mouse models of human neurological conditions. In this review, we summarize the current state-of-the-art of RNAi and its utility to neuroscientists.
Topics: Animals; Genetic Therapy; Humans; Models, Biological; Nervous System Diseases; Nervous System Physiological Phenomena; RNA Interference; RNA, Small Interfering
PubMed: 17359914
DOI: 10.1016/j.neuron.2007.02.020 -
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 -
Journal of Insect Physiology Jun 2023The whitefly Bemisia tabaci is a globally important crop pest that is difficult to manage through current commercially available methods. While RNA interference (RNAi)...
The whitefly Bemisia tabaci is a globally important crop pest that is difficult to manage through current commercially available methods. While RNA interference (RNAi) is a promising strategy for managing this pest, effective target genes remain unclear. We suggest DNA methyltransferase 1 (Dnmt1) as a potential target gene due to its effect on fecundity in females in other taxa of insects. We investigated the role of Dnmt1 in B. tabaci using RNAi and immunohistochemistry to confirm its potential conserved function in insect reproduction, which will define its usefulness as a target gene. Using RNAi to downregulate Dnmt1 in female B. tabaci, we show that Dnmt1 indeed has a conserved role in reproduction, as knockdown interfered with oocyte development. Females in which Dnmt1 was knocked down had greatly reduced fecundity and fertility; this supports Dnmt1 as a suitable target gene for RNAi-mediated pest management of B. tabaci.
Topics: Animals; Female; Genes, Insect; Insect Control; Hemiptera; Reproduction; RNA Interference; Oocytes
PubMed: 37011857
DOI: 10.1016/j.jinsphys.2023.104507 -
Nucleic Acid Therapeutics Jun 2012The manifestation of RNA interference (RNAi)-based therapeutics lies in safe and successful delivery of small interfering RNAs (siRNAs), the molecular entity that... (Review)
Review
The manifestation of RNA interference (RNAi)-based therapeutics lies in safe and successful delivery of small interfering RNAs (siRNAs), the molecular entity that triggers and guides sequence-specific degradation of target mRNAs. Optimizing the chemistry and structure of siRNAs to achieve maximum efficacy is an important parameter in the development of siRNA therapeutics. The RNAi protein machinery can tolerate a variety of non-canonical modifications made to siRNAs, each of which imparts advantageous properties. Here, we review these modifications to siRNAs in pre-clinical and clinical studies.
Topics: Clinical Trials as Topic; Humans; RNA Interference; RNA, Small Interfering
PubMed: 22703279
DOI: 10.1089/nat.2012.0361 -
Molecules (Basel, Switzerland) Apr 2021RNA interference (RNAi) can mediate gene-silencing by knocking down the expression of a target gene via cellular machinery with much higher efficiency in contrast to... (Review)
Review
RNA interference (RNAi) can mediate gene-silencing by knocking down the expression of a target gene via cellular machinery with much higher efficiency in contrast to other antisense-based approaches which represents an emerging therapeutic strategy for combating cancer. Distinct characters of nanoparticles, such as distinctive size, are fundamental for the efficient delivery of RNAi therapeutics, allowing for higher targeting and safety. In this review, we present the mechanism of RNAi and briefly describe the hurdles and concerns of RNAi as a cancer treatment approach in systemic delivery. Furthermore, the current nanovectors for effective tumor delivery of RNAi therapeutics are classified, and the characteristics of different nanocarriers are summarized.
Topics: Animals; Drug Delivery Systems; Humans; Nanoparticles; Neoplasms; RNA Interference
PubMed: 33921892
DOI: 10.3390/molecules26082380 -
Current Opinion in Chemical Biology Oct 2021RNA has long been an enticing therapeutic target, but is now garnering increased attention, largely driven by clinical successes of RNA interference-based drugs. While... (Review)
Review
RNA has long been an enticing therapeutic target, but is now garnering increased attention, largely driven by clinical successes of RNA interference-based drugs. While gene knockdown by well-established RNA interference- and other oligonucleotide-based strategies continues to advance in the clinic, the repertoire of targetable effectors capable of altering gene expression at the RNA level is also rapidly expanding. In this review, we focus on several recently developed bifunctional molecular technologies that both interact with and act upon a target RNA. These new approaches for programmable RNA knockdown, editing, splicing, translation, and chemical modifications stand to provide impactful new modalities for therapeutic development in the coming decades.
Topics: CRISPR-Cas Systems; Gene Editing; Gene Expression; RNA; RNA Interference
PubMed: 33930627
DOI: 10.1016/j.cbpa.2021.03.004 -
Journal of Visualized Experiments : JoVE May 2018Phloem and plant sap feeding insects invade the integrity of crops and fruits to retrieve nutrients, in the process damaging food crops. Hemipteran insects account for a...
Phloem and plant sap feeding insects invade the integrity of crops and fruits to retrieve nutrients, in the process damaging food crops. Hemipteran insects account for a number of economically substantial pests of plants that cause damage to crops by feeding on phloem sap. The brown marmorated stink bug (BMSB), Halyomorpha halys (Heteroptera: Pentatomidae) and the Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Liviidae) are hemipteran insect pests introduced in North America, where they are an invasive agricultural pest of high-value specialty, row, and staple crops and citrus fruits, as well as a nuisance pest when they aggregate indoors. Insecticide resistance in many species has led to the development of alternate methods of pest management strategies. Double-stranded RNA (dsRNA)-mediated RNA interference (RNAi) is a gene silencing mechanism for functional genomic studies that has potential applications as a tool for the management of insect pests. Exogenously synthesized dsRNA or small interfering RNA (siRNA) can trigger highly efficient gene silencing through the degradation of endogenous RNA, which is homologous to that presented. Effective and environmental use of RNAi as molecular biopesticides for biocontrol of hemipteran insects requires the in vivo delivery of dsRNAs through feeding. Here we demonstrate methods for delivery of dsRNA to insects: loading of dsRNA into green beans by immersion, and absorbing of gene-specific dsRNA with oral delivery through ingestion. We have also outlined non-transgenic plant delivery approaches using foliar sprays, root drench, trunk injections as well as clay granules, all of which may be essential for sustained release of dsRNA. Efficient delivery by orally ingested dsRNA was confirmed as an effective dosage to induce a significant decrease in expression of targeted genes, such as juvenile hormone acid O-methyltransferase (JHAMT) and vitellogenin (Vg). These innovative methods represent strategies for delivery of dsRNA to use in crop protection and overcome environmental challenges for pest management.
Topics: Administration, Oral; Animals; Hemiptera; Insecta; Phloem; RNA Interference; RNA, Double-Stranded
PubMed: 29782023
DOI: 10.3791/57390 -
International Journal of Molecular... Dec 2020RNA interference (RNAi) was discovered at the end of last millennium, changing the way scientists understood regulation of gene expression. Within the following two... (Review)
Review
RNA interference (RNAi) was discovered at the end of last millennium, changing the way scientists understood regulation of gene expression. Within the following two decades, a variety of different RNAi mechanisms were found in eukaryotes, reflecting the evolutive diversity that RNAi entails. The essential silencing mechanism consists of an RNase III enzyme called Dicer that cleaves double-stranded RNA (dsRNA) generating small interfering RNAs (siRNAs), a hallmark of RNAi. These siRNAs are loaded into the RNA-induced silencing complex (RISC) triggering the cleavage of complementary messenger RNAs by the Argonaute protein, the main component of the complex. Consequently, the expression of target genes is silenced. This mechanism has been thoroughly studied in fungi due to their proximity to the animal phylum and the conservation of the RNAi mechanism from lower to higher eukaryotes. However, the role and even the presence of RNAi differ across the fungal kingdom, as it has evolved adapting to the particularities and needs of each species. Fungi have exploited RNAi to regulate a variety of cell activities as different as defense against exogenous and potentially harmful DNA, genome integrity, development, drug tolerance, or virulence. This pathway has offered versatility to fungi through evolution, favoring the enormous diversity this kingdom comprises.
Topics: Evolution, Molecular; Fungi; Gene Expression Regulation, Fungal; RNA Interference
PubMed: 33302447
DOI: 10.3390/ijms21249348 -
The Plant Genome Dec 2023As conserved regulatory agents, noncoding RNAs (ncRNAs) have an important impact on many aspects of plant life, including growth, development, and environmental... (Review)
Review
As conserved regulatory agents, noncoding RNAs (ncRNAs) have an important impact on many aspects of plant life, including growth, development, and environmental response. Noncoding RNAs can travel through not only plasmodesma and phloem but also intercellular barriers to regulate distinct processes. Increasing evidence shows that the intercellular trans-kingdom transmission of ncRNAs is able to modulate many important interactions between plants and other organisms, such as plant response to pathogen attack, the symbiosis between legume plants and rhizobia and the interactions with parasitic plants. In these interactions, plant ncRNAs are believed to be sorted into extracellular vesicles (EVs) or other nonvesicular vehicles to pass through cell barriers and trigger trans-kingdom RNA interference (RNAi) in recipient cells from different species. There is evidence that the features of extracellular RNAs and associated RNA-binding proteins (RBPs) play a role in defining the RNAs to retain in cell or secrete outside cells. Despite the few reports about RNA secretion pathway in plants, the export of extracellular ncRNAs is orchestrated by a series of pathways in plants. The identification and functional analysis of mobile small RNAs (sRNAs) are attracting increasing attention in recent years. In this review, we discuss recent advances in our understanding of the function, sorting, transport, and regulation of plant extracellular ncRNAs.
Topics: Gene-Environment Interaction; RNA Interference; RNA, Untranslated; RNA, Plant; Plants
PubMed: 36444889
DOI: 10.1002/tpg2.20289 -
Trends in Biotechnology Jul 2021European Union (EU) and global sustainability policies emphasize the need to replace contentious pesticides with safe, efficient, and cost-effective alternatives to... (Review)
Review
European Union (EU) and global sustainability policies emphasize the need to replace contentious pesticides with safe, efficient, and cost-effective alternatives to ensure sustainable food production. However, R&D for alternatives to contentious pesticides are lagging behind and need to be broadened. Here, we discuss how RNAi-based technology can contribute to pesticide risk reduction.
Topics: Agriculture; European Union; Goals; Pest Control; Pesticides; RNA Interference; Sustainable Growth; Technology
PubMed: 33288312
DOI: 10.1016/j.tibtech.2020.11.008