A particular set of small non-coding RNAs is bound to the distinctive Argonaute protein of Trypanosoma cruzi: Insights from RNA-interference deficient organisms

Gene ◽  
2014 ◽  
Vol 538 (2) ◽  
pp. 379-384 ◽  
Author(s):  
Maria Rosa Garcia-Silva ◽  
Julia Sanguinetti ◽  
Florencia Cabrera-Cabrera ◽  
Oscar Franzén ◽  
Alfonso Cayota
Keyword(s):  
Rna Interference ◽  
Trypanosoma Cruzi ◽  
Argonaute Protein ◽  
Non Coding Rnas

scholarly journals Targeting Inflammasome Activation in COVID-19: Delivery of RNA Interference-Based Therapeutic Molecules

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1823
Author(s):  
Lealem Gedefaw ◽  
Sami Ullah ◽  
Thomas M. H. Lee ◽  
Shea Ping Yip ◽  
Chien-Ling Huang
Keyword(s):  
Rna Interference ◽  
Effective Treatment ◽  
Critical Role ◽  
Treatment Strategies ◽  
Drug Efficacy ◽  
Immune Dysregulation ◽  
Inflammasome Activation ◽  
Mortality And Morbidity ◽  
Therapeutic Molecules ◽  
Non Coding Rnas

Mortality and morbidity associated with COVID-19 continue to be significantly high worldwide, owing to the absence of effective treatment strategies. The emergence of different variants of SARS-CoV-2 is also a considerable source of concern and has led to challenges in the development of better prevention and treatment strategies, including vaccines. Immune dysregulation due to pro-inflammatory mediators has worsened the situation in COVID-19 patients. Inflammasomes play a critical role in modulating pro-inflammatory cytokines in the pathogenesis of COVID-19 and their activation is associated with poor clinical outcomes. Numerous preclinical and clinical trials for COVID-19 treatment using different approaches are currently underway. Targeting different inflammasomes to reduce the cytokine storm, and its associated complications, in COVID-19 patients is a new area of research. Non-coding RNAs, targeting inflammasome activation, may serve as an effective treatment strategy. However, the efficacy of these therapeutic agents is highly dependent on the delivery system. MicroRNAs and long non-coding RNAs, in conjunction with an efficient delivery vehicle, present a potential strategy for regulating NLRP3 activity through various RNA interference (RNAi) mechanisms. In this regard, the use of nanomaterials and other vehicle types for the delivery of RNAi-based therapeutic molecules for COVID-19 may serve as a novel approach for enhancing drug efficacy. The present review briefly summarizes immune dysregulation and its consequences, the roles of different non-coding RNAs in regulating the NLRP3 inflammasome, distinct types of vectors for their delivery, and potential therapeutic targets of microRNA for treatment of COVID-19.

scholarly journals DIRS retrotransposons amplify via linear, single-stranded cDNA intermediates

2020 ◽  
Vol 48 (8) ◽  
pp. 4230-4243 ◽  
Author(s):  
Marek Malicki ◽  
Thomas Spaller ◽  
Thomas Winckler ◽  
Christian Hammann
Keyword(s):  
Rna Interference ◽  
Rna Polymerase ◽  
Dictyostelium Discoideum ◽  
Repeat Sequence ◽  
Marker Genes ◽  
Argonaute Protein ◽  
Tyrosine Recombinase ◽  
Rna Dependent Rna Polymerase ◽  
Rna Transcripts ◽  
Complementary Region

Abstract The Dictyostelium Intermediate Repeat Sequence 1 (DIRS-1) is the name-giving member of the DIRS order of tyrosine recombinase retrotransposons. In Dictyostelium discoideum, DIRS-1 is highly amplified and enriched in heterochromatic centromers of the D. discoideum genome. We show here that DIRS-1 it tightly controlled by the D. discoideum RNA interference machinery and is only mobilized in mutants lacking either the RNA dependent RNA polymerase RrpC or the Argonaute protein AgnA. DIRS retrotransposons contain an internal complementary region (ICR) that is thought to be required to reconstitute a full-length element from incomplete RNA transcripts. Using different versions of D. discoideum DIRS-1 equipped with retrotransposition marker genes, we show experimentally that the ICR is in fact essential to complete retrotransposition. We further show that DIRS-1 produces a mixture of single-stranded, mostly linear extrachromosomal cDNA intermediates. If this cDNA is isolated and transformed into D. discoideum cells, it can be used by DIRS-1 proteins to complete productive retrotransposition. This work provides the first experimental evidence to propose a general retrotransposition mechanism of the class of DIRS like tyrosine recombinase retrotransposons.

scholarly journals Phloem-mediated spreading of SIGS-derived non-coding RNAs in Hordeum vulgare

2019 ◽  
Author(s):  
D Biedenkopf ◽  
T Will ◽  
T Knauer ◽  
L Jelonek ◽  
ACU Furch ◽  
...  
Keyword(s):  
Rna Interference ◽  
Host Defense ◽  
Vascular System ◽  
Control Plant ◽  
Plant Diseases ◽  
Long Distance ◽  
Rnai Machinery ◽  
Rna Molecules ◽  
Non Coding Rnas ◽  
Long Distance Movement

AbstractSmall (s)RNA molecules are crucial factors in the communication between hosts and their interacting pathogens/pests that can modulate both host defense and microbial virulence/pathogenicity known as cross-kingdom RNA interference (ckRNAi). Consistent with this, sRNAs and their double-stranded (ds)RNA precursors have been adopted to control plant diseases through exogenously applied RNA biopesticides, known as spray-induced gene silencing (SIGS). While RNA spray proved to be effective, the mechanisms underlying the transfer and uptake of SIGS-associated RNAs are inadequately understood. Moreover, the use of the SIGS-technology as a biopesticide will require the systemic spreading of dsRNA/siRNA signals. Our results strongly support the notion of phloem-mediated long-distance movement of SIGS-associated dsRNA and/or siRNA. These findings are significant contributions to our mechanistic understanding of RNA spray technology, as our previous data indicate that SIGS requires the processing of dsRNAs by the fungal RNAi machinery. In summary, our findings support the model that SIGS involves: (i) uptake of sprayed dsRNA by the plant (via stomata); (ii) transfer of apoplastic dsRNAs into the symplast (DCL processing into siRNAs); (iii) systemic translocation of siRNA or unprocessed dsRNA via the vascular system (phloem/xylem); (iv) uptake of apoplastic dsRNA or symplastic dsRNA/siRNA depending on the lifestyle/feeding behavior of the pathogen/pest.

Cloning, characterization and subcellular localization of a Trypanosoma cruzi argonaute protein defining a new subfamily distinctive of trypanosomatids

Gene ◽  
2010 ◽  
Vol 466 (1-2) ◽  
pp. 26-35 ◽  
Author(s):  
Maria R. Garcia Silva ◽  
Juan P. Tosar ◽  
Magali Frugier ◽  
Sergio Pantano ◽  
Braulio Bonilla ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Subcellular Localization ◽  
Argonaute Protein

3. RNA

2016 ◽  
Author(s):  
Aysha Divan ◽  
Janice A. Royds
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Rna Interference ◽  
Ribosomal Rna ◽  
Gene Function ◽  
Transfer Rna ◽  
Vast Number ◽  
Rna Molecules ◽  
Catalytic Rnas ◽  
Non Coding Rnas

The first RNA molecules to be discovered were those involved in protein synthesis, mRNA, transfer RNA (tRNA), and ribosomal RNA (rRNA). In recent years, a vast number of additional RNA molecules have been identified. ‘RNA’ explains that these are non-coding RNAs that are not involved in protein synthesis, but influence many normal cellular and disease processes by regulating gene expression. RNA interference (RNAi) as one of the main ways in which gene expression is regulated is described with applications to therapy. Classes of RNA, including long non-coding RNAs and catalytic RNAs, are explained along with RNA techniques used to study RNA molecule and gene function.

Secondary siRNAs Result from Unprimed RNA Synthesis and Form a Distinct Class

Science ◽  
2006 ◽  
Vol 315 (5809) ◽  
pp. 244-247 ◽  
Author(s):  
Titia Sijen ◽  
Florian A. Steiner ◽  
Karen L. Thijssen ◽  
Ronald H. A. Plasterk
Keyword(s):  
Rna Interference ◽  
Small Rnas ◽  
Rna Synthesis ◽  
Argonaute Protein ◽  
Single Nucleotide ◽  
Distinct Class ◽  
C Elegans ◽  
Secondary Sirnas ◽  
Secondary Sirna ◽  
Rnai Response

In Caenorhabditis elegans, an effective RNA interference (RNAi) response requires the production of secondary short interfering RNAs (siRNAs) by RNA-directed RNA polymerases (RdRPs). We cloned secondary siRNAs from transgenic C. elegans lines expressing a single 22-nucleotide primary siRNA. Several secondary siRNAs start a few nucleotides downstream of the primary siRNA, indicating that non–RISC (RNA-induced silencing complex)–cleaved mRNAs are substrates for secondary siRNA production. In lines expressing primary siRNAs with single-nucleotide mismatches, secondary siRNAs do not carry the mismatch but contain the nucleotide complementary to the mRNA. We infer that RdRPs perform unprimed RNA synthesis. Secondary siRNAs are only of antisense polarity, carry 5′ di- or triphosphates, and are only in the minority associated with RDE-1, the RNAi-specific Argonaute protein. Therefore, secondary siRNAs represent a distinct class of small RNAs. Their biogenesis depends on RdRPs, and we propose that each secondary siRNA is an individual RdRP product.

scholarly journals Cross-Kingdom Small RNAs Among Animals, Plants and Microbes

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 371 ◽  
Author(s):  
Zeng ◽  
Gupta ◽  
Jiang ◽  
Yang ◽  
Gong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Interference ◽  
Gene Silencing ◽  
Horizontal Transfer ◽  
Small Rnas ◽  
Signal Transmission ◽  
Fungal Diseases ◽  
Small Interfering Rnas ◽  
Eukaryotic Species ◽  
Non Coding Rnas

Small RNAs (sRNAs), a class of regulatory non-coding RNAs around 20~30-nt long, including small interfering RNAs (siRNAs) and microRNAs (miRNAs), are critical regulators of gene expression. Recently, accumulating evidence indicates that sRNAs can be transferred not only within cells and tissues of individual organisms, but also across different eukaryotic species, serving as a bond connecting the animal, plant, and microbial worlds. In this review, we summarize the results from recent studies on cross-kingdom sRNA communication. We not only review the horizontal transfer of sRNAs among animals, plants and microbes, but also discuss the mechanism of RNA interference (RNAi) signal transmission via cross-kingdom sRNAs. We also compare the advantages of host-induced gene silencing (HIGS) and spray-induced gene silencing (SIGS) technology and look forward to their applicable prospects in controlling fungal diseases.

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