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A chemogenomic screening identifies CK2 as a target for pro-senescence therapy in PTEN-deficient tumours
It has been proposed that the identification of genes regulating senescence in the absence of PTEN might help develop pro-senescence compounds for the treatment of cancer. Here, the authors use a combination of chemical and shRNA functional screen and identify CK2 as a potential target.
- Madhuri Kalathur
- , Alberto Toso
- & Andrea Alimonti
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eIF1A augments Ago2-mediated Dicer-independent miRNA biogenesis and RNA interference
miRNAs are incorporated into ribonucleoprotein complexes called RNA-induced silencing complexes (RISCs) to exert RNA interference. Here the authors show that translation initiation factor eIF1A interacts with the RISCs component Ago2 to promote miR-451 biogenesis and RNA interference.
- Tingfang Yi
- , Haribabu Arthanari
- & Gerhard Wagner
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RNAi-based functional selection identifies novel cell migration determinants dependent on PI3K and AKT pathways
Large-scale genetic screens combined with phenotype assays can identify novel regulators of specific cellular functions. Here, Seo et al. use shRNA-based genetic selection to identify novel genes regulating cell migration, functioning within the PI 3-kinase/PTEN/AKT signalling pathway.
- Minchul Seo
- , Shinrye Lee
- & Kyoungho Suk
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Macromolecular structures probed by combining single-shot free-electron laser diffraction with synchrotron coherent X-ray imaging
Macromolecular complexes hold promise for future generations of drug delivery carriers, but probing their structures with high resolution is challenging. Here, the authors combine X-ray free-electron laser and synchrotron approaches to reveal the core-shell structure of RNA interference microsponges.
- Marcus Gallagher-Jones
- , Yoshitaka Bessho
- & Changyong Song
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Genome-wide RNAi ionomics screen reveals new genes and regulation of human trace element metabolism
The composition of trace elements in human cells (the ionome) is an important component of metabolism. Here, the authors carry out a high-throughput, genome-wide analysis of the human ionome and identify cellular regulators of important trace elements such as selenium, copper and iron.
- Mikalai Malinouski
- , Nesrin M. Hasan
- & Vadim N. Gladyshev
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Phytochrome RNAi enhances major fibre quality and agronomic traits of the cotton Gossypium hirsutum L
Improving the quality of cotton fibres is important for agriculture and fibre length is influenced by far-red light. Here, the authors knock down the red/far-red photoreceptor Phytocrome A1 of cotton and show that this enhances cotton fibre length.
- Ibrokhim Y. Abdurakhmonov
- , Zabardast T. Buriev
- & Alan E. Pepper
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An influenza virus-inspired polymer system for the timed release of siRNA
Small interfering RNA is degraded by plasma and can’t cross the cell membrane due to its negative charge. Here, the authors present an influenza inspired polymer carrier, capable of local RNA delivery, which degrades to a non-toxic by-product, and is thus suitable for multiple doses.
- Nghia P Truong
- , Wenyi Gu
- & Michael J Monteiro
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| Open AccessTargeted suppression of claudin-5 decreases cerebral oedema and improves cognitive outcome following traumatic brain injury
Claudin-5 is a component of tight junctions and has important roles in mediating the permeability of the blood-brain barrier. Campbell and co-workers administer short interfering RNA against claudin-5 in a model of brain injury, finding that it enhances water movement from the brain to the blood and alleviates swelling.
- Matthew Campbell
- , Finnian Hanrahan
- & Peter Humphries
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Inhibition of specific gene expressions by protein-mediated mRNA interference
RNA can be silenced in a sequence-specific manner but whether proteins can silence RNA in this way is unknown. Now, Yamaguchi and colleagues show that an enzyme isolated fromHaloquadra walsbyi cleaves 7-base-pair sequences in Escherichia coli, and this high sequence specificity permits the silencing of targeted genes.
- Yoshihiro Yamaguchi
- , Hirofumi Nariya
- & Masayori Inouye
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SIRT6 is required for maintenance of telomere position effect in human cells
Chromatin is rendered silent by epigenetic marks when in proximity to telomeres, and, in yeast, this effect requires the histone-modifying enzyme Sir2. In this study, the human Sir2 family member SIRT6 is shown to modulate the telomere position effect in human cells.
- Ruth I. Tennen
- , Dennis J. Bua
- & Katrin F. Chua
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| Open AccessToxicity modelling of Plk1-targeted therapies in genetically engineered mice and cultured primary mammalian cells
Polo-like kinase 1 is a key regulator of mitosis and is a candidate for drug development to treat cancer. Here, reduced expression of polo-like kinase 1 in adult mice has a minor impact on animal physiology, suggesting that polo-like kinase 1 inhibitors may be useful in the killing of tumour cells while sparing normal cells.
- Monika Raab
- , Sven Kappel
- & Klaus Strebhardt