Intracellular small interfering RNA delivery using genetically engineered double-stranded RNA binding protein domain

2009 ◽  
Vol 11 (9) ◽  
pp. 804-812 ◽  
Author(s):  
Juwon Kim ◽  
Soo Hyeon Lee ◽  
Joonho Choe ◽  
Tae Gwan Park
2018 ◽  
Vol 115 (33) ◽  
pp. 8334-8339 ◽  
Author(s):  
June-Sun Yoon ◽  
Kanakachari Mogilicherla ◽  
Dhandapani Gurusamy ◽  
Xien Chen ◽  
Shankar C. R. R. Chereddy ◽  
...  

RNA interference (RNAi) is being used to develop methods to control pests and disease vectors. RNAi is robust and systemic in coleopteran insects but is quite variable in other insects. The determinants of efficient RNAi in coleopterans, as well as its potential mechanisms of resistance, are not known. RNAi screen identified a double-stranded RNA binding protein (StaufenC) as a major player in RNAi. StaufenC homologs have been identified in only coleopteran insects. Experiments in two coleopteran insects, Leptinotarsa decemlineata and Tribolium castaneum, showed the requirement of StaufenC for RNAi, especially for processing of double-stranded RNA (dsRNA) to small interfering RNA. RNAi-resistant cells were selected by exposing L. decemlineata, Lepd-SL1 cells to the inhibitor of apoptosis 1 dsRNA for multiple generations. The resistant cells showed lower levels of StaufenC expression compared with its expression in susceptible cells. These studies showed that coleopteran-specific StaufenC is required for RNAi and is a potential target for RNAi resistance. The data included in this article will help improve RNAi in noncoleopteran insects and manage RNAi resistance in coleopteran insects.


2013 ◽  
Vol 87 (24) ◽  
pp. 13409-13421 ◽  
Author(s):  
J. E. Petrillo ◽  
P. A. Venter ◽  
J. R. Short ◽  
R. Gopal ◽  
S. Deddouche ◽  
...  

Virology ◽  
1993 ◽  
Vol 195 (2) ◽  
pp. 732-744 ◽  
Author(s):  
Hao Yuwen ◽  
Josephine H. Cox ◽  
Jonathan W. Yewdell ◽  
Jack R. Bennink ◽  
Bernard Moss

2016 ◽  
Vol 130 (1) ◽  
pp. 45-55 ◽  
Author(s):  
Hikaru Sawano ◽  
Takuma Matsuzaki ◽  
Tomoyuki Usui ◽  
Midori Tabara ◽  
Akihito Fukudome ◽  
...  

2007 ◽  
Vol 28 (2) ◽  
pp. 772-783 ◽  
Author(s):  
Frank Vumbaca ◽  
Kathryn N. Phoenix ◽  
Daniel Rodriguez-Pinto ◽  
David K. Han ◽  
Kevin P. Claffey

ABSTRACT Vascular endothelial growth factor (VEGF) is a key angiogenic factor expressed under restricted nutrient and oxygen conditions in most solid tumors. The expression of VEGF under hypoxic conditions requires transcription through activated hypoxia-inducible factor 1 (HIF-1), increased mRNA stability, and facilitated translation. This study identified double-stranded RNA-binding protein 76/NF90 (DRBP76/NF90), a specific isoform of the DRBP family, as a VEGF mRNA-binding protein which plays a key role in VEGF mRNA stability and protein synthesis under hypoxia. The DRBP76/NF90 protein binds to a human VEGF 3′ untranslated mRNA stability element. RNA interference targeting the DRBP76/NF90 isoform limited hypoxia-inducible VEGF mRNA and protein expression with no change in HIF-1-dependent transcriptional activity. Stable repression of DRBP76/NF90 in MDA-MB-435 breast cancer cells demonstrated reduced polysome-associated VEGF mRNA levels under hypoxic conditions and reduced mRNA stability. Transient overexpression of the DRBP76/NF90 protein increased both VEGF mRNA and protein levels synthesized under normoxic and hypoxic conditions. Cells with stable repression of the DRBP76/NF90 isoform showed reduced tumorigenic and angiogenic potential in an orthotopic breast tumor model. These data demonstrate that the DRBP76/NF90 isoform facilitates VEGF expression by promoting VEGF mRNA loading onto polysomes and translation under hypoxic conditions, thus promoting breast cancer growth and angiogenesis in vivo.


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