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Microbiology Spectrum Dec 2016RNA interference (RNAi) is a mechanism conserved in eukaryotes, including fungi, that represses gene expression by means of small noncoding RNAs (sRNAs) of about 20 to... (Review)
Review
RNA interference (RNAi) is a mechanism conserved in eukaryotes, including fungi, that represses gene expression by means of small noncoding RNAs (sRNAs) of about 20 to 30 nucleotides. Its discovery is one of the most important scientific breakthroughs of the past 20 years, and it has revolutionized our perception of the functioning of the cell. Initially described and characterized in Neurospora crassa, the RNAi is widespread in fungi, suggesting that it plays important functions in the fungal kingdom. Several RNAi-related mechanisms for maintenance of genome integrity, particularly protection against exogenous nucleic acids such as mobile elements, have been described in several fungi, suggesting that this is the main function of RNAi in the fungal kingdom. However, an increasing number of fungal sRNAs with regulatory functions generated by specific RNAi pathways have been identified. Several mechanistic aspects of the biogenesis of these sRNAs are known, but their function in fungal development and physiology is scarce, except for remarkable examples such as Mucor circinelloides, in which specific sRNAs clearly regulate responses to environmental and endogenous signals. Despite the retention of RNAi in most species, some fungal groups and species lack an active RNAi mechanism, suggesting that its loss may provide some selective advantage. This article summarizes the current understanding of RNAi functions in the fungal kingdom.
Topics: Fungi; Gene Expression Regulation, Fungal; RNA Interference; RNA, Fungal
PubMed: 28087943
DOI: 10.1128/microbiolspec.FUNK-0008-2016 -
Journal of Virology Nov 2014The question of whether any mammalian cells are able to mount an effective RNA interference-mediated antiviral innate immune response has remained highly controversial.... (Review)
Review
The question of whether any mammalian cells are able to mount an effective RNA interference-mediated antiviral innate immune response has remained highly controversial. In this Gem, I review recent data addressing this important issue and propose a testable hypothesis that can explain many of the apparently contradictory results published in this area of research.
Topics: Animals; Humans; RNA Interference; RNA, Viral; Viruses
PubMed: 25210170
DOI: 10.1128/JVI.01179-14 -
Current Neuropharmacology 2021Neurodegenerative diseases (ND), as a group of central nervous system (CNS) disorders, are among the most prominent medical problems of the 21st century. They are often... (Review)
Review
Neurodegenerative diseases (ND), as a group of central nervous system (CNS) disorders, are among the most prominent medical problems of the 21st century. They are often associated with considerable disability, motor dysfunction and dementia and are more common in the aged population. ND imposes a psychologic, economic and social burden on the patients and their families. Currently, there is no effective treatment for ND. Since many ND result from the gain of function of a mutant allele, small interference RNA (siRNA) can be a potential therapeutic agent for ND management. Based on the RNA interference (RNAi) approach, siRNA is a powerful tool for modulating gene expression through gene silencing. However, there are some obstacles in the clinical application of siRNA, including unfavorable immune response, off-target effects, instability of naked siRNA, nuclease susceptibility and a need to develop a suitable delivery system. Since there are some issues related to siRNA delivery routes, in this review, we focus on the application of siRNA in the management of ND treatment from 2000 to 2020.
Topics: Aged; Gene Silencing; Humans; Neoplasms; Neurodegenerative Diseases; RNA Interference; RNA, Small Interfering
PubMed: 33797386
DOI: 10.2174/1570159X19666210402104054 -
The New Phytologist Jul 2021Host-induced gene silencing (HIGS) technology has emerged as a powerful alternative to chemical treatments for protecting plants from pathogens or pests. More than 170... (Review)
Review
Host-induced gene silencing (HIGS) technology has emerged as a powerful alternative to chemical treatments for protecting plants from pathogens or pests. More than 170 HIGS studies have been published so far, and HIGS products have been launched. First, we discuss the strengths and limitations of this technology in a pathosystem-specific context. Next, we highlight the requirement for fundamental knowledge on the molecular mechanisms (i.e. uptake, processing and translocation of transgene-expressed double-stranded RNAs) that determine the efficacy and specificity of HIGS. Additionally, we speculate on the contribution of host and target RNA interference machineries, which may be incompatible depending on the lifestyle of the pathogen or pest. Finally, we predict that closing these gaps in knowledge will lead to the development of novel integrative concepts, precise risk assessment and tailor-made HIGS therapy for plant diseases.
Topics: Gene Silencing; Plant Diseases; Plants; RNA Interference; RNA, Double-Stranded
PubMed: 33774815
DOI: 10.1111/nph.17364 -
Philosophical Transactions of the Royal... Nov 2018Genomes are under constant threat of invasion by transposable elements and other genomic parasites. How can host genomes recognize these elements and target them for... (Review)
Review
Genomes are under constant threat of invasion by transposable elements and other genomic parasites. How can host genomes recognize these elements and target them for degradation? This requires a system that is highly adaptable, and at the same time highly specific. Current data suggest that perturbation of transcription patterns by transposon insertions could be detected by the RNAi surveillance pathway. Multiple transposon insertions might generate sufficient amounts of primal small RNAs to initiate generation of secondary small RNAs and silencing. At the same time primal small RNAs need to be constantly degraded to reduce the level of noise small RNAs below the threshold required for initiation of silencing. Failure in RNA degradation results in loss of fidelity of small RNA pathways and silencing of ectopic targets.This article is part of the theme issue '5' and 3' modifications controlling RNA degradation'.
Topics: DNA Transposable Elements; Eukaryota; RNA; RNA Interference
PubMed: 30397104
DOI: 10.1098/rstb.2018.0168 -
Practical Neurology Apr 2018Many genetic neurological diseases result from the dysfunction of single proteins. Genetic therapies aim to modify these disease-associated proteins by targeting the RNA... (Review)
Review
Many genetic neurological diseases result from the dysfunction of single proteins. Genetic therapies aim to modify these disease-associated proteins by targeting the RNA and DNA precursors. This review provides a brief overview of the main types of genetic therapies, with a focus on antisense oligonucleotides (ASOs) and RNA interference (RNAi). We use examples of new genetic therapies for spinal muscular atrophy, Duchenne muscular dystrophy and familial amyloid polyneuropathy to highlight the different mechanisms of action of ASOs and RNAi.
Topics: Genetic Therapy; Humans; Oligodeoxyribonucleotides, Antisense; RNA Interference
PubMed: 29455156
DOI: 10.1136/practneurol-2017-001764 -
FEMS Microbiology Reviews May 2015The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) adaptive immune systems use small guide RNAs, the CRISPR RNAs (crRNAs), to... (Review)
Review
The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) adaptive immune systems use small guide RNAs, the CRISPR RNAs (crRNAs), to mark foreign genetic material, e.g. viral nucleic acids, for degradation. Archaea and bacteria encode a large variety of Cas proteins that bind crRNA molecules and build active ribonucleoprotein surveillance complexes. The evolution of CRISPR-Cas systems has resulted in a diversification of cas genes and a classification of the systems into three types and additional subtypes characterized by distinct surveillance and interfering complexes. Recent crystallographic and biochemical advances have revealed detailed insights into the assembly and DNA/RNA targeting mechanisms of the various complexes. Here, we review our knowledge on the molecular mechanism involved in the DNA and RNA interference stages of type I (Cascade: CRISPR-associated complex for antiviral defense), type II (Cas9) and type III (Csm, Cmr) CRISPR-Cas systems. We further highlight recently reported structural and mechanistic themes shared among these systems.
Topics: CRISPR-Cas Systems; DNA, Bacterial; Evolution, Molecular; Genetic Variation; RNA Interference; Ribonucleoproteins
PubMed: 25934119
DOI: 10.1093/femsre/fuv019 -
Journal of Controlled Release :... Nov 2022RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA)... (Review)
Review
RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA) mediate sequence-specific mRNA degradation. RNAi technology has recently emerged as a promising therapeutic platform for the effective treatment of various diseases caused by inappropriate gene activity, such as cancer. However, the clinical translation of siRNA therapeutics has been hampered by the major hurdles associated with biological instability and limited delivery efficiency. Based on the various efforts, recent siRNA delivery strategies using cationic lipids and polymers allowed to enhance pharmacokinetics and delivery efficiency, resulting in potent and liver-targeted RNAi therapy. However, non-specific protein adsorption, high liver accumulation, and severe toxicity of cationic nanocarriers still limit the possibility of transfer of siRNA therapeutics from the laboratory to the clinic. One of the promising delivery strategies to overcome the limitations of siRNA therapeutics is carrier-free bioconjugation which is chemically modified and connected with biocompatible molecules such as lipids, peptides, antibodies, aptamers, and polymers. These molecularly engineered siRNA conjugates can be utilized for RNAi delivery to tissues beyond the liver, providing opportunities for clinical translation. This review focused on introducing the recent progress in molecularly engineered siRNA conjugates and their applications toward overcoming the limitations of siRNA for tumor-targeted delivery and therapy.
Topics: Humans; RNA, Small Interfering; RNAi Therapeutics; RNA, Double-Stranded; RNA Interference; Neoplasms; Polymers; Lipids
PubMed: 36152808
DOI: 10.1016/j.jconrel.2022.09.040 -
Advanced Drug Delivery Reviews Jul 2021Ribonucleic acid interference (RNAi) is an innovative treatment strategy for a myriad of indications. Non-viral synthetic nanoparticles (NPs) have drawn extensive... (Review)
Review
Ribonucleic acid interference (RNAi) is an innovative treatment strategy for a myriad of indications. Non-viral synthetic nanoparticles (NPs) have drawn extensive attention as vectors for RNAi due to their potential advantages, including improved safety, high delivery efficiency and economic feasibility. However, the complex natural process of RNAi and the susceptible nature of oligonucleotides render the NPs subject to particular design principles and requirements for practical fabrication. Here, we summarize the requirements and obstacles for fabricating non-viral nano-vectors for efficient RNAi. To address the delivery challenges, we discuss practical guidelines for materials selection and NP synthesis in order to maximize RNA encapsulation efficiency and protection against degradation, and to facilitate the cytosolic release of oligonucleotides. The current status of clinical translation of RNAi-based therapies and further perspectives for reducing the potential side effects are also reviewed.
Topics: Animals; Gene Transfer Techniques; Humans; Nanoparticles; Oligonucleotides; RNA Interference; RNA, Small Interfering
PubMed: 34019958
DOI: 10.1016/j.addr.2021.05.018 -
Acta Biochimica Polonica 2016Natural antisense transcripts (NATs) are RNA molecules that originate from opposite DNA strands of the same genomic locus (cis-NAT) or unlinked genomic loci (trans-NAT).... (Review)
Review
Natural antisense transcripts (NATs) are RNA molecules that originate from opposite DNA strands of the same genomic locus (cis-NAT) or unlinked genomic loci (trans-NAT). NATs may play various regulatory functions at the transcriptional level via transcriptional interference. NATs may also regulate gene expression levels post-transcriptionally via induction of epigenetic changes or double-stranded RNA formation, which may lead to endogenous RNA interference, RNA editing or RNA masking. The true biological significance of the natural antisense transcripts remains controversial despite many years of research. Here, we summarize the current state of knowledge and discuss the sense-antisense overlap regulatory mechanisms and their potential.
Topics: Animals; Humans; Promoter Regions, Genetic; RNA Editing; RNA Interference; RNA, Small Interfering; Transcription, Genetic
PubMed: 27770572
DOI: 10.18388/abp.2016_1350