Disease relevance of RNA Interference

• Conversely, knockdown of PRAME expression by RNA interference in RA-resistant human melanoma restores RAR signaling and reinstates sensitivity to the antiproliferative effects of RA in vitro and in vivo [1].
• Tetanus toxin-mediated inactivation of Gr68a-expressing neurons or transgene-mediated RNA interference of Gr68a RNA leads to a significant reduction in male courtship performance, suggesting that GR68a protein is an essential component of pheromone-driven courtship behavior in Drosophila [2].
• Knockdown of PARP-1 by RNA interference significantly suppressed both transcriptional activity and proliferation by colorectal cancer cells [3].
• By retrovirus infection and small interference RNA, we generated SHP overexpressing and SHP-deficient HSC-T6 [4].
• Functional analysis using RNA interference (RNAi) and combinations of insertion alleles revealed a role for the AML genes in meiosis, with RNAi lines and specific multiple mutant combinations displaying sterility and a range of defects in meiotic chromosome behavior [5].

High impact information on RNA Interference

• In vivo RNA interference demonstrates a role for Nramp1 in modifying susceptibility to type 1 diabetes [6].
• We show here that components of the RNA interference (RNAi) machinery are involved in PcG-mediated silencing at Fab-7 and in the production of small RNAs at transgenic Fab-7 copies [7].
• DRD3 is a functionally diversified homolog of NRPD1a or SDE4, identified in a separate screen for mutants defective in post-transcriptional gene silencing [8].
• The mRNA-cleavage step of RNA interference is mediated by an endonuclease, Argonaute2 (Ago2), within the RNA-induced silencing complex (RISC) [9].
• Using a Gal4-induced RNA interference system, we showed that conditional depletion of HP1 in transgenic flies resulted in preferential lethality in male flies [10].

Chemical compound and disease context of RNA Interference

• Conversely, silencing of ENH by RNA interference prevents cytoplasmic relocation of Id2 in neuroblastoma cells differentiated with retinoic acid [11].
• Decreased TAF7 expression, by RNA interference, in androgen-independent human prostate cancer LN-CaP104-R1 cells resulted in lower polyamine transport activity (25% of control) and resistance to MGBG-induced growth arrest [12].
• Induction of G0/G1 cell cycle arrest in ovarian carcinoma cells by the anti-inflammatory drug NS-398, but not by COX-2-specific RNA interference [13].
• RNA interference demonstrates a novel role for integrin-linked kinase as a determinant of pancreatic adenocarcinoma cell gemcitabine chemoresistance [14].
• Evidence for a piwi-dependent RNA silencing of the gypsy endogenous retrovirus by the Drosophila melanogaster flamenco gene [15].

Biological context of RNA Interference

• Elimination of Mule expression by RNA interference stabilizes Mcl-1 protein, resulting in an attenuation of the apoptosis induced by DNA-damage agents [16].
• The sde1 mutation was specific for posttranscriptional gene silencing induced by transgenes rather than by viruses [17].
• Furthermore, our analyses suggest that RNA interference machinery operates in cis as a stable component of heterochromatic domains with RITS tethered to silenced loci by methylation of histone H3 at Lys9 [18].
• Recent advances have led to a more detailed understanding of RNA interference and its role in microRNA biogenesis and function [19].
• Importantly, depletion of haspin by RNA interference reveals that this kinase is required for H3 Thr 3 phosphorylation in mitotic cells [20].

Anatomical context of RNA Interference

• Using RNA interference in synchronized HeLa cells, we now show that Aurora-A is required for mitotic entry [21].
• Mutations in dlt or double-stranded RNA interference lead to aberrant localization of CRB and NRX IV and cause a concomitant loss of epithelial cell polarity [22].
• We demonstrate that Apoptin expression, or depletion of APC1 by RNA interference, inhibits APC/C function in p53 null cells, resulting in G2/M arrest and apoptosis [23].
• Using RNA interference and ectopic expression of constitutively activated forms of STAT5, we demonstrate here a function for STAT5 in the self-renewal of B cells in vitro [24].
• Specific knockdown of HDAC2 by RNA interference resulted in reduced sensitivity to dexamethasone suppression of interleukin 1beta-induced granulocyte/macrophage colony-stimulating factor production [25].

Associations of RNA Interference with chemical compounds

• Here we evaluate the ability of RNA interference (RNAi) to inhibit polyglutamine-induced neurodegeneration caused by mutant ataxin-1 in a mouse model of SCA1 [26].
• Through RNA interference (RNAi)-based screening of serine/threonine phosphatases in Drosophila S2 cells, we identified pyruvate dehydrogenase phosphatase (PDP) to be required for dephosphorylation of Mothers against Decapentaplegic (MAD), a Drosophila Smad [27].
• We used RNA interference (RNAi) to interfere with BDNF expression, and tyrosine kinase receptor inhibition to block BDNF signaling [28].
• RNA interference (RNAi) of GGA3 expression results in accumulation of the cation-independent mannose 6-phosphate receptor and internalized epidermal growth factor (EGF) within enlarged early endosomes [29].
• RNA interference (RNAi) demonstrates that MEKK3 and the scaffold protein are required for p38 activation in response to sorbitol-induced hyperosmolarity [30].

Gene context of RNA Interference

• To address the biological function of RNA interference (RNAi)-related pathways in mammals, we disrupted the gene Dicer1 in mice [31].
• The rde-1 gene, RNA interference, and transposon silencing in C. elegans [32].
• Arabidopsis SGS2 and SGS3 genes are required for posttranscriptional gene silencing and natural virus resistance [33].
• Depletion of PEN-2 by RNA interference prevents endoproteolysis of presenilin and promotes stabilization of the holoprotein in both Drosophila and mammalian cells, including primary neurons [34].
• Here we show that AGO2 is an essential component for siRNA-directed RNA interference (RNAi) response and is required for the unwinding of siRNA duplex and in consequence assembly of siRNA into RISC in Drosophila embryos [35].

Analytical, diagnostic and therapeutic context of RNA Interference

• Here we ablate hRIP activity with a dominant-negative mutant or RNA interference and analyze Rev function by RNA in situ hybridization [36].
• Here we use Drosophila melanogaster S2 cells expressing alpha-tubulin tagged with green fluorescent protein, RNA interference, laser microsurgery and photobleaching to show that the kinetochore protein MAST/Orbit - the single CLASP orthologue in Drosophila - is an essential component for microtubule subunit incorporation into fluxing K-fibres [37].
• METHODS: To test this hypothesis we used the technique of RNA interference to inhibit MCT1 expression specifically, and determined the consequences of this inhibition on the ability of butyrate to exert its recognized effects in vitro using flow cytometry, immunofluorescence, Northern analysis, and Western analysis [38].
• Using immunofluorescence with a variety of p160ROCK antibodies, immuno EM, and depletion with RNA interference, p160ROCK is principally bound to the mother centriole (MC) and an intercentriolar linker [39].
• Here, we developed a cell culture model in which the RNA interference (RNAi) technology was used to deplete a potential component of Fe/S protein maturation, frataxin, in human HeLa cells [40].

References