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Nature Cell Biology Dec 2022The endoplasmic reticulum (ER) coordinates mRNA translation and processing of secreted and endomembrane proteins. ER-associated degradation (ERAD) prevents the...
The endoplasmic reticulum (ER) coordinates mRNA translation and processing of secreted and endomembrane proteins. ER-associated degradation (ERAD) prevents the accumulation of misfolded proteins in the ER, but the physiological regulation of this process remains poorly characterized. Here, in a genetic screen using an ERAD model substrate in Caenorhabditis elegans, we identified an anti-viral RNA interference pathway, referred to as ER-associated RNA silencing (ERAS), which acts together with ERAD to preserve ER homeostasis and function. Induced by ER stress, ERAS is mediated by the Argonaute protein RDE-1/AGO2, is conserved in mammals and promotes ER-associated RNA turnover. ERAS and ERAD are complementary, as simultaneous inactivation of both quality-control pathways leads to increased ER stress, reduced protein quality control and impaired intestinal integrity. Collectively, our findings indicate that ER homeostasis and organismal health are protected by synergistic functions of ERAS and ERAD.
Topics: RNA Interference; Endoplasmic Reticulum
PubMed: 36471127
DOI: 10.1038/s41556-022-01025-4 -
International Journal of Molecular... Dec 2022MicroRNAs (miRNAs) act as master regulators of gene expression in homeostasis and disease. Despite the rapidly growing body of evidence on the theranostic potential of... (Review)
Review
MicroRNAs (miRNAs) act as master regulators of gene expression in homeostasis and disease. Despite the rapidly growing body of evidence on the theranostic potential of restoring miRNA levels in pre-clinical models, the translation into clinics remains limited. Here, we review the current knowledge of miRNAs as T-cell targeting immunotherapeutic tools, and we offer an overview of the recent advances in miRNA delivery strategies, clinical trials and future perspectives in RNA interference technologies.
Topics: MicroRNAs; T-Lymphocytes; RNA Interference; Precision Medicine; Immunotherapy
PubMed: 36613706
DOI: 10.3390/ijms24010250 -
International Journal of Molecular... Jun 2023Antisense RNA was observed to elicit plant disease resistance and post-translational gene silencing (PTGS). The universal mechanism of RNA interference (RNAi) was shown... (Review)
Review
Antisense RNA was observed to elicit plant disease resistance and post-translational gene silencing (PTGS). The universal mechanism of RNA interference (RNAi) was shown to be induced by double-stranded RNA (dsRNA), an intermediate produced during virus replication. Plant viruses with a single-stranded positive-sense RNA genome have been instrumental in the discovery and characterization of systemic RNA silencing and suppression. An increasing number of applications for RNA silencing have emerged involving the exogenous application of dsRNA through spray-induced gene silencing (SIGS) that provides specificity and environmentally friendly options for crop protection and improvement.
Topics: RNA Interference; Gene Silencing; RNA, Double-Stranded; RNA, Small Interfering; Plants; Plant Diseases
PubMed: 37298705
DOI: 10.3390/ijms24119755 -
Nature Oct 2019
Topics: Clinical Trials as Topic; Genetic Diseases, Inborn; Genetic Therapy; Humans; RNA; RNA Interference
PubMed: 31619808
DOI: 10.1038/d41586-019-03067-5 -
Nature Chemical Biology Jul 2022
Topics: Cell Line; RNA Interference
PubMed: 35761077
DOI: 10.1038/s41589-022-01078-4 -
Chemistry, An Asian Journal Aug 2022RNA interference (RNAi) is a primitive evolutionary mechanism developed to escape incorporation of foreign genetic material. siRNA has been instrumental in achieving the... (Review)
Review
RNA interference (RNAi) is a primitive evolutionary mechanism developed to escape incorporation of foreign genetic material. siRNA has been instrumental in achieving the therapeutic potential of RNAi by theoretically silencing any gene of interest in a reversible and sequence-specific manner. Extrinsically administered siRNA generally needs a delivery vehicle to span across different physiological barriers and load into the RISC complex in the cytoplasm in its functional form to show its efficacy. This review discusses the designing principles and examples of different classes of delivery vehicles that have proved to be efficient in RNAi therapeutics. We also briefly discuss the role of RNAi therapeutics in genetic and rare diseases, epigenetic modifications, immunomodulation and combination modality to inch closer in creating a personalized therapy for metastatic cancer. At the end, we present, strategies and look into the opportunities to develop efficient delivery vehicles for RNAi which can be translated into clinics.
Topics: Cytoplasm; Humans; Neoplasms; RNA Interference; RNA, Small Interfering; RNAi Therapeutics
PubMed: 35689534
DOI: 10.1002/asia.202200451 -
Nature Reviews. Genetics May 2020Declines in bee populations across the world threaten food security and ecosystem function. It is currently not possible to routinely predict which specific stressors... (Review)
Review
Declines in bee populations across the world threaten food security and ecosystem function. It is currently not possible to routinely predict which specific stressors lead to declines in different populations or contexts, hindering efforts to improve bee health. Genomics has the potential to dramatically improve our ability to identify, monitor and predict the effects of stressors, as well as to mitigate their impacts through the use of marker-assisted selection, RNA interference and potentially gene editing. Here we discuss the most compelling recent applications of genomics to investigate the mechanisms underpinning bee population declines and to improve the health of both wild and managed bee populations.
Topics: Animals; Bees; Gene Editing; Genomics; RNA Interference; Stress, Physiological
PubMed: 32099102
DOI: 10.1038/s41576-020-0216-1 -
Wiley Interdisciplinary Reviews. RNA Jan 2023The clustered regularly interspaced short palindromic repeats (CRISPR) system is a product of million years of evolution by microbes to fight against invading genetic... (Review)
Review
The clustered regularly interspaced short palindromic repeats (CRISPR) system is a product of million years of evolution by microbes to fight against invading genetic materials. Around 10 years ago, scientists started to repurpose the CRISPR as genetic tools by molecular engineering approaches. The guide RNA provides a versatile and unique platform for the innovation to improve and expand the application of CRISPR-Cas9 system. In this review, we will first introduce the basic sequence and structure of guide RNA and its role during the function of CRISPR-Cas9. We will then summarize recent progress on the development of various guide RNA engineering strategies. These strategies have been dedicated to improve the performance of CRISPR-Cas9, to achieve precise spatiotemporal control of CRISPR-Cas9, and to broaden the application of CRISPR-Cas9. Finally, we will briefly discuss the uniqueness and advantage of guide RNA-engineering based systems versus those with engineered Cas9 proteins and speculate potential future directions in guide RNA engineering. This article is categorized under: RNA Methods > RNA Analyses In Vitro and In Silico RNA Methods > RNA Nanotechnology Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.
Topics: CRISPR-Cas Systems; RNA; RNA Interference; Genetic Engineering; RNA, Guide, CRISPR-Cas Systems
PubMed: 35393779
DOI: 10.1002/wrna.1731 -
Annual Review of Virology Sep 2021Viroids are small, single-stranded, circular RNAs infecting plants. Composed of only a few hundred nucleotides and being unable to code for proteins, viroids represent... (Review)
Review
Viroids are small, single-stranded, circular RNAs infecting plants. Composed of only a few hundred nucleotides and being unable to code for proteins, viroids represent the lowest level of complexity for an infectious agent, even below that of the smallest known viruses. Despite the relatively small size, viroids contain RNA structural elements embracing all the information needed to interact with host factors involved in their infectious cycle, thus providing models for studying structure-function relationships of RNA. Viroids are specifically targeted to nuclei (family ) or chloroplasts (family ), where replication based on rolling-circle mechanisms takes place. They move locally and systemically through plasmodesmata and phloem, respectively, and may elicit symptoms in the infected host, with pathogenic pathways linked to RNA silencing and other plant defense responses. In this review, recent advances in the dissection of the complex interplay between viroids and plants are presented, highlighting knowledge gaps and perspectives for future research.
Topics: Plant Diseases; Plants; RNA Interference; RNA, Viral; Viroids
PubMed: 34255541
DOI: 10.1146/annurev-virology-091919-092331 -
Virologie (Montrouge, France) Dec 2020A key aspect of antiviral immunity is the distinction between "self" and "non-self" components. This distinction can be established through the detection of... (Review)
Review
A key aspect of antiviral immunity is the distinction between "self" and "non-self" components. This distinction can be established through the detection of double-stranded RNA (dsRNA), a common sign of viral infection, by cytosolic RNA helicases. Depending on the organism, two major antiviral pathways can be induced by dsRNA helicases: RNA interference (RNAi) and interferon (IFN) signaling. In the RNAi pathway, dsRNAs are recognized by a Dicer protein, and are then used for the sequence-dependent recognition and subsequent degradation of the complementary viral RNAs. In the IFN signaling pathway, dsRNAs are recognized by a RIG-like receptor (RLR), which induces a signaling cascade in order to induce the expression of IFNs, cytokines and chemokines. In this review, we discuss the RNA features that can be used by the cell to detect a viral infection, the two aforementioned types of helicase-mediated sensing, as well as some viral escape mechanisms developed to avoid recognition.
Topics: Humans; Interferons; RNA Interference; RNA, Double-Stranded; Signal Transduction; Virus Diseases
PubMed: 33441288
DOI: 10.1684/vir.2020.0872