scholarly journals Drosophila Dicer-2 has an RNA interference–independent function that modulates Toll immune signaling

2015 ◽  
Vol 1 (9) ◽  
pp. e1500228 ◽  
Author(s):  
Zhaowei Wang ◽  
Di Wu ◽  
Yongxiang Liu ◽  
Xiaoling Xia ◽  
Wanyun Gong ◽  
...  
Keyword(s):  
Rna Interference ◽  
Posttranscriptional Regulation ◽  
Protein Translation ◽  
Binding Activity ◽  
Rnai Pathway ◽  
Independent Function ◽  
Immune Signaling ◽  
Toll Signaling ◽  
Rna Biogenesis ◽  
Interfering Rna

Dicer-2 is the central player for small interfering RNA biogenesis in the Drosophila RNA interference (RNAi) pathway. Intriguingly, we found that Dicer-2 has an unconventional RNAi-independent function that positively modulates Toll immune signaling, which defends against Gram-positive bacteria, fungi, and some viruses, in both cells and adult flies. The loss of Dicer-2 expression makes fruit flies more susceptible to fungal infection. We further revealed that Dicer-2 posttranscriptionally modulates Toll signaling because Dicer-2 is required for the proper expression of Toll protein but not for Toll protein stability or Toll mRNA transcription. Moreover, Dicer-2 directly binds to the 3′ untranslated region (3′UTR) of Toll mRNA via its PAZ (Piwi/Argonaute/Zwille) domain and is required for protein translation mediated by Toll 3′UTR. The loss of Toll 3′UTR binding activity makes Dicer-2 incapable of promoting Toll signaling. These data indicate that the interaction between Dicer-2 and Toll mRNA plays a pivotal role in Toll immune signaling. In addition, we found that Dicer-2 is also required for the Toll signaling induced by two different RNA viruses in Drosophila cells. Consequently, our findings uncover a novel RNAi-independent function of Dicer-2 in the posttranscriptional regulation of Toll protein expression and signaling, indicate an unexpected intersection of the RNAi pathway and the Toll pathway, and provide new insights into Toll immune signaling, Drosophila Dicer-2, and probably Dicer and Dicer-related proteins in other organisms.

scholarly journals Small Interfering RNA- Modern Approach for Intervening Pathological Conditions

2021 ◽  
Vol 2 (2) ◽  
pp. 16-19
Author(s):  
Shazia Choudhary ◽  
Sheeba Murad ◽  
Sana Gul ◽  
Hayat Khan ◽  
Samra Khalid ◽  
...  
Keyword(s):  
Rna Interference ◽  
Small Interfering Rna ◽  
Sirna Delivery ◽  
Rnai Pathway ◽  
Modern Approach ◽  
Rna Molecules ◽  
Rnai Technology ◽  
Efficient Delivery ◽  
Biological Discovery ◽  
Interfering Rna

RNA interference (RNAi) refers to the inhibition of gene expression by small double-stranded RNA molecules. This technology can prove to be a breakthrough biological discovery of the decade as it has the potential to revolutionize the field of therapeutics. RNA interference (RNAi) through small interfering RNA (siRNA) is currently being evaluated for its efficacy to be used in therapeutics as well as prophylactic strategies. Many studies are being conducted across the globe to optimize the siRNA delivery systems (in terms of safe, stable and efficient delivery) in various disorders. There are a number of diseases such as autoimmune diseases, cancer associated pathological changes, bacterial and viral induced disorders, where RNAi pathway can be explored and RNAi technology can be used as a tool to intervene such abnormalities. This review is an effort to review latest advancements in the field of siRNA based therapy development and the pits and falls generally encountered in the use of this technology.

The development of RNA interference (RNAi) in gastrointestinal nematodes

Parasitology ◽  
2012 ◽  
Vol 139 (5) ◽  
pp. 605-612 ◽  
Author(s):  
MURRAY E. SELKIRK ◽  
STANLEY C. HUANG ◽  
DAVID P. KNOX ◽  
COLLETTE BRITTON
Keyword(s):  
Rna Interference ◽  
Gene Transcription ◽  
Mode Of Delivery ◽  
Gastrointestinal Nematodes ◽  
Rnai Pathway ◽  
Parasitic Nematodes ◽  
Future Directions ◽  
C Elegans ◽  
Unpublished Work ◽  
Interfering Rna

SUMMARYDespite the utility of RNAi for defining gene function in Caenorhabditis elegans and early successes reported in parasitic nematodes, RNAi has proven to be stubbornly inconsistent or ineffective in the animal parasitic nematodes examined to date. Here, we summarise some of our experiences with RNAi in parasitic nematodes affecting animals and discuss the available data in the context of our own unpublished work, taking account of mode of delivery, larval activation, site of gene transcription and the presence/absence of essential RNAi pathway genes as defined by comparisons to C. elegans. We discuss future directions briefly including the evaluation of nanoparticles as a means to enhance delivery of interfering RNA to the target worm tissue.

scholarly journals Impact of Two Reoviruses and Their Coinfection on the Rice RNAi System and vsiRNA Production

Viruses ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 594 ◽  
Author(s):  
Zhanbiao Li ◽  
Tong Zhang ◽  
Xiuqin Huang ◽  
Guohui Zhou
Keyword(s):  
Rna Interference ◽  
Hot Spots ◽  
Rna Polymerases ◽  
The Other ◽  
Dwarf Virus ◽  
Rnai Pathway ◽  
The Family ◽  
Synergistic Mechanism ◽  
Interfering Rna ◽  
Rice Ragged Stunt Virus

Both Southern rice black-streaked dwarf virus (SRBSDV) and Rice ragged stunt virus (RRSV) belong to the family Reoviridae, and synergistic infection of these two viruses commonly occurs in the field. This study revealed that both SRBSDV and RRSV affect the RNA interference (RNAi) pathway and form different virus-derived interfering RNA (vsiRNA) profiles in rice. Co-infection of rice by SRBSDV and RRSV up-regulated the expression of rice DICER-like (DCL) proteins but down-regulated the expression of rice RNA-dependent RNA polymerases (RDRs), and the accumulation of vsiRNAs of either RBSDV or RRSV was decreased compared with that in singly infected plants. The majority of SRBSDV vsiRNAs were 21 nt or 22 nt in length, whether plants were singly infected with SRBSDV or co-infected with RRSV. On the other hand, the majority of RRSV vsiRNAs were 20 nt, 21 nt, or 22 nt in length, among which those 20 nt in length accounted for the largest proportion; co-infection with SRBSDV further increased the proportion of 20 nt vsiRNAs and decreased the proportion of 21 nt vsiRNAs. Co-infection had no effects on the strand favoritism and hot spots of the vsiRNAs, but changed the bias of the 5′ terminal nucleotide significantly. This study provides a reference for further study on the pathogenesis and synergistic mechanism of SRBSDV and RRSV.

scholarly journals Amphiphysin 1 Is Important for Actin Polymerization during Phagocytosis

2007 ◽  
Vol 18 (11) ◽  
pp. 4669-4680 ◽  
Author(s):  
Hiroshi Yamada ◽  
Emiko Ohashi ◽  
Tadashi Abe ◽  
Norihiro Kusumi ◽  
Shun-AI Li ◽  
...  
Keyword(s):  
Rna Interference ◽  
Sertoli Cells ◽  
Small Interfering Rna ◽  
Actin Polymerization ◽  
Actin Dynamics ◽  
Polymerization Process ◽  
Amphiphysin 1 ◽  
Phagocytic Cups ◽  
Interfering Rna ◽  
Constitutively Active

Amphiphysin 1 is involved in clathrin-mediated endocytosis. In this study, we demonstrate that amphiphysin 1 is essential for cellular phagocytosis and that it is critical for actin polymerization. Phagocytosis in Sertoli cells was induced by stimulating phosphatidylserine receptors. This stimulation led to the formation of actin-rich structures, including ruffles, phagocytic cups, and phagosomes, all of which showed an accumulation of amphiphysin 1. Knocking out amphiphysin 1 by RNA interference in the cells resulted in the reduction of ruffle formation, actin polymerization, and phagocytosis. Phagocytosis was also drastically decreased in amph 1 (−/−) Sertoli cells. In addition, phosphatidylinositol-4,5-bisphosphate–induced actin polymerization was decreased in the knockout testis cytosol. The addition of recombinant amphiphysin 1 to the cytosol restored the polymerization process. Ruffle formation in small interfering RNA-treated cells was recovered by the expression of constitutively active Rac1, suggesting that amphiphysin 1 functions upstream of the protein. These findings support that amphiphysin 1 is important in the regulation of actin dynamics and that it is required for phagocytosis.

scholarly journals PBRM1 Cooperates with YTHDF2 to Control HIF-1α Protein Translation

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1425
Author(s):  
Alena Shmakova ◽  
Mark Frost ◽  
Michael Batie ◽  
Niall S. Kenneth ◽  
Sonia Rocha
Keyword(s):  
Protein Expression ◽  
Cellular Response ◽  
Transcriptional Activity ◽  
Mrna Translation ◽  
Protein Translation ◽  
Signalling Pathways ◽  
Independent Function ◽  
Protein Levels ◽  
Associated Proteins ◽  
Core Components

PBRM1, a component of the chromatin remodeller SWI/SNF, is often deleted or mutated in human cancers, most prominently in renal cancers. Core components of the SWI/SNF complex have been shown to be important for the cellular response to hypoxia. Here, we investigated how PBRM1 controls HIF-1α activity. We found that PBRM1 is required for HIF-1α transcriptional activity and protein levels. Mechanistically, PBRM1 is important for HIF-1α mRNA translation, as absence of PBRM1 results in reduced actively translating HIF-1α mRNA. Interestingly, we found that PBRM1, but not BRG1, interacts with the m6A reader protein YTHDF2. HIF-1α mRNA is m6A-modified, bound by PBRM1 and YTHDF2. PBRM1 is necessary for YTHDF2 binding to HIF-1α mRNA and reduction of YTHDF2 results in reduced HIF-1α protein expression in cells. Our results identify a SWI/SNF-independent function for PBRM1, interacting with HIF-1α mRNA and the epitranscriptome machinery. Furthermore, our results suggest that the epitranscriptome-associated proteins play a role in the control of hypoxia signalling pathways.

scholarly journals Saccharomyces cerevisiae (Baker’s Yeast) as an Interfering RNA Expression and Delivery System

2019 ◽  
Vol 20 (9) ◽  
pp. 942-952 ◽  
Author(s):  
Molly Duman-Scheel
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Rna Interference ◽  
Genetic Model ◽  
Model Organism ◽  
Rna Expression ◽  
Commercial Development ◽  
Rna Integrity ◽  
Yeast Cultures ◽  
Ideal System ◽  
Interfering Rna

The broad application of RNA interference for disease prevention is dependent upon the production of dsRNA in an economically feasible, scalable, and sustainable fashion, as well as the identification of safe and effective methods for RNA delivery. Current research has sparked interest in the use of Saccharomyces cerevisiae for these applications. This review examines the potential for commercial development of yeast interfering RNA expression and delivery systems. S. cerevisiae is a genetic model organism that lacks a functional RNA interference system, which may make it an ideal system for expression and accumulation of high levels of recombinant interfering RNA. Moreover, recent studies in a variety of eukaryotic species suggest that this microbe may be an excellent and safe system for interfering RNA delivery. Key areas for further research and development include optimization of interfering RNA expression in S. cerevisiae, industrial-sized scaling of recombinant yeast cultures in which interfering RNA molecules are expressed, the development of methods for largescale drying of yeast that preserve interfering RNA integrity, and identification of encapsulating agents that promote yeast stability in various environmental conditions. The genetic tractability of S. cerevisiae and a long history of using this microbe in both the food and pharmaceutical industry will facilitate further development of this promising new technology, which has many potential applications of medical importance.

DrosophilaoncogeneGas41is an RNA interference modulator that intersects heterochromatin and the small interfering RNA pathway

FEBS Journal ◽  
2014 ◽  
Vol 282 (1) ◽  
pp. 153-173 ◽  
Author(s):  
Sumit G. Gandhi ◽  
Indira Bag ◽  
Saswati Sengupta ◽  
Manika Pal-Bhadra ◽  
Utpal Bhadra
Keyword(s):  
Rna Interference ◽  
Small Interfering Rna ◽  
Interfering Rna

scholarly journals RNA Interference of Human Papillomavirus Type 18 E6 and E7 Induces Senescence in HeLa Cells

2003 ◽  
Vol 77 (10) ◽  
pp. 6066-6069 ◽  
Author(s):  
Allison H. S. Hall ◽  
Kenneth A. Alexander
Keyword(s):  
Cell Proliferation ◽  
Human Papillomavirus ◽  
Rna Interference ◽  
Hela Cells ◽  
Tumor Suppressors ◽  
Small Interfering Rna ◽  
Promote Cell Proliferation ◽  
E6 And E7 ◽  
Cellular Dna ◽  
Interfering Rna

ABSTRACT The human papillomavirus oncoproteins E6 and E7 promote cell proliferation and contribute to carcinogenesis by interfering with the activities of cellular tumor suppressors. We used a small interfering RNA molecule targeting the E7 region of the bicistronic E6 and E7 mRNA to induce RNA interference, thereby reducing expression of E6 and E7 in HeLa cells. RNA interference of E6 and E7 also inhibited cellular DNA synthesis and induced morphological and biochemical changes characteristic of cellular senescence. These results demonstrate that reducing E6 and E7 expression is sufficient to cause HeLa cells to become senescent.

scholarly journals FOXO regulates RNA interference in Drosophila and protects from RNA virus infection

2015 ◽  
Vol 112 (47) ◽  
pp. 14587-14592 ◽  
Author(s):  
Michael J. Spellberg ◽  
Michael T. Marr
Keyword(s):  
Rna Interference ◽  
Virus Infection ◽  
Gene Silencing ◽  
Small Rna ◽  
Stress Responses ◽  
Posttranscriptional Regulation ◽  
Rna Virus ◽  
Regulation Of Gene Expression ◽  
Cellular Physiology ◽  
Metabolic Conditions

Small RNA pathways are important players in posttranscriptional regulation of gene expression. These pathways play important roles in all aspects of cellular physiology from development to fertility to innate immunity. However, almost nothing is known about the regulation of the central genes in these pathways. The forkhead box O (FOXO) family of transcription factors is a conserved family of DNA-binding proteins that responds to a diverse set of cellular signals. FOXOs are crucial regulators of cellular homeostasis that have a conserved role in modulating organismal aging and fitness. Here, we show that Drosophila FOXO (dFOXO) regulates the expression of core small RNA pathway genes. In addition, we find increased dFOXO activity results in an increase in RNA interference (RNAi) efficacy, establishing a direct link between cellular physiology and RNAi. Consistent with these findings, dFOXO activity is stimulated by viral infection and is required for effective innate immune response to RNA virus infection. Our study reveals an unanticipated connection among dFOXO, stress responses, and the efficacy of small RNA-mediated gene silencing and suggests that organisms can tune their gene silencing in response to environmental and metabolic conditions.

Sign in / Sign up

Export Citation Format

Share Document