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 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 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 Structurally modulated codelivery of siRNA and Argonaute 2 for enhanced RNA interference

2018 ◽  
Vol 115 (12) ◽  
pp. E2696-E2705 ◽  
Author(s):  
Jiahe Li ◽  
Connie Wu ◽  
Wade Wang ◽  
Yanpu He ◽  
Elad Elkayam ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Rna Interference ◽  
Small Interfering Rna ◽  
Sirna Delivery ◽  
Effector Protein ◽  
Side Group ◽  
Argonaute 2 ◽  
Fundamental Research ◽  
Delivery Vehicles ◽  
Interfering Rna

Small interfering RNA (siRNA) represents a promising class of inhibitors in both fundamental research and the clinic. Numerous delivery vehicles have been developed to facilitate siRNA delivery. Nevertheless, achieving highly potent RNA interference (RNAi) toward clinical translation requires efficient formation of RNA-induced gene-silencing complex (RISC) in the cytoplasm. Here we coencapsulate siRNA and the central RNAi effector protein Argonaute 2 (Ago2) via different delivery carriers as a platform to augment RNAi. The physical clustering between siRNA and Ago2 is found to be indispensable for enhanced RNAi. Moreover, by utilizing polyamines bearing the same backbone but distinct cationic side-group arrangements of ethylene diamine repeats as the delivery vehicles, we find that the molecular structure of these polyamines modulates the degree of siRNA/Ago2-mediated improvement of RNAi. We apply this strategy to silence the oncogene STAT3 and significantly prolong survival in mice challenged with melanoma. Our findings suggest a paradigm for RNAi via the synergistic coassembly of RNA with helper proteins.

scholarly journals Antiviral Effects of Small Interfering RNA Simultaneously Inducing RNA Interference and Type 1 Interferon in Coxsackievirus Myocarditis

2012 ◽  
Vol 56 (7) ◽  
pp. 3516-3523 ◽  
Author(s):  
Jeonghyun Ahn ◽  
Ara Ko ◽  
Eun Jung Jun ◽  
Minah Won ◽  
Yoo Kyum Kim ◽  
...  
Keyword(s):  
Rna Interference ◽  
Small Interfering Rna ◽  
Antiviral Treatment ◽  
Coxsackievirus B3 ◽  
Hydroxyl Group ◽  
Specific Gene ◽  
Type I ◽  
Antiviral Effects ◽  
Direct Demonstration ◽  
Interfering Rna

ABSTRACTAntiviral therapeutics are currently unavailable for treatment of coxsackievirus B3, which can cause life-threatening myocarditis. A modified small interfering RNA (siRNA) containing 5′-triphosphate, 3p-siRNA, was shown to induce RNA interference and interferon activation. We aimed to develop a potent antiviral treatment using CVB3-specific 3p-siRNA and to understand its underlying mechanisms. Virus-specific 3p-siRNA was superior to both conventional virus-specific siRNA with an empty hydroxyl group at the 5′ end (OH-siRNA) and nonspecific 3p-siRNA in decreasing viral replication and subsequent cytotoxicity. A single administration of 3p-siRNA dramatically attenuated virus-associated pathological symptoms in mice with no signs of toxicity, and their body weights eventually reached the normal range. Myocardial inflammation and fibrosis were rare, and virus production was greatly reduced. A nonspecific 3p-siRNA showed relatively less protective effect under identical conditions, and a virus-specific OH-siRNA showed no protective effects. We confirmed that virus-specific 3p-siRNA simultaneously activated target-specific gene silencing and type I interferon signaling. We provide a clear proof of concept that coxsackievirus B3-specific 3p-siRNA has 2 distinct modes of action, which significantly enhance antiviral activities with minimal organ damage. This is the first direct demonstration of improved antiviral effects with an immunostimulatory virus-specific siRNA in coxsackievirus myocarditis, and this method could be applied to many virus-related diseases.

scholarly journals Effects of small interfering RNA interference of connexin 37 on subcutaneous gastric tumours in mice

2014 ◽  
Vol 10 (6) ◽  
pp. 2955-2960 ◽  
Author(s):  
YUANMING JING ◽  
SUXIA GUO ◽  
XIAOPING ZHANG ◽  
AIJING SUN ◽  
FENG TAO ◽  
...  
Keyword(s):  
Rna Interference ◽  
Small Interfering Rna ◽  
Connexin 37 ◽  
Interfering Rna

scholarly journals Interferencja RNA w terapii genowej nowotworów rejonu głowy i szyi

2016 ◽  
Vol 13 (3) ◽  
pp. 64-72
Author(s):  
Agnieszka Sobecka ◽  
Wojciech Barczak ◽  
Wiktoria Maria Suchorska
Keyword(s):  
Squamous Cell Carcinoma ◽  
Rna Interference ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Small Interfering Rna ◽  
Neck Squamous Cell Carcinoma ◽  
Interfering Rna

Rak płaskonabłonkowy rejonu głowy i szyi (HNSCC, ang. Head and Neck Squamous Cell Carcinoma) jest szóstym najczęściej występującym nowotworem na świecie. Leczenie tego typu nowotworów polega głównie na stosowaniu metod chirurgicznych uzupełnionych pooperacyjną chemio- i/lub radioterapią. Prowadzone są też badania nad zastosowaniem terapii genowej poprzez wykorzystanie zjawiska interferencji RNA (RNAi, ang. RNA interference). RNAi  jest efektywnym narzędziem w terapii wielu chorób, takich jak zakażenia wirusowe, cukrzyca czy choroby neurodegeneracyjne. Wykazano, że cząsteczki siRNA (krótkie interferujące RNA, ang. small interfering RNA) oraz miRNA (mikroRNA, ang. microRNA) zaangażowane są w regulację wielu patologicznych procesów zachodzących podczas nowotworzenia. RNAi stała się zatem cennym narzędziem badawczym pozwalającym na lepsze poznanie mechanizmów regulujących patogenezę raka. Uważa się również, że dzięki swojej wysokiej specyficzności, zjawisko RNAi może być użytecznym narzędziem w terapii genowej nowotworów. Niniejsza praca stanowi przegląd aktualnej wiedzy na temat możliwości wykorzystania RNAi w leczeniu nowotworów rejonu głowy i szyi.

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