Abstract:
:RNA interference has become an indispensable tool for loss-of-function studies across eukaryotes. By enabling stable and reversible gene silencing, shRNAs provide a means to study long-term phenotypes, perform pool-based forward genetic screens and examine the consequences of temporary target inhibition in vivo. However, efficient implementation in vertebrate systems has been hindered by technical difficulties affecting potency and specificity. Focusing on these issues, we analyse current strategies to obtain maximal knockdown with minimal off-target effects.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Fellmann C,Lowe SWdoi
10.1038/ncb2895subject
Has Abstractpub_date
2014-01-01 00:00:00pages
10-8issue
1eissn
1465-7392issn
1476-4679pii
ncb2895journal_volume
16pub_type
杂志文章,评审abstract::Primary cilia are required for vertebrate cells to respond to specific intercellular signals. Here we define when and where primary cilia appear in the mouse embryo using a transgenic line that expresses ARL13B-mCherry in cilia and Centrin 2-GFP in centrosomes. Primary cilia first appear on cells of the epiblast at E6...
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abstract::The seminal observation that mechanical signals can elicit changes in biochemical signalling within cells, a process commonly termed mechanosensation and mechanotransduction, has revolutionized our understanding of the role of cell mechanics in various fundamental biological processes, such as cell motility, adhesion,...
journal_title:Nature cell biology
pub_type: 杂志文章,评审
doi:10.1038/ncb3524
更新日期:2017-05-31 00:00:00
abstract::Topoisomerase II (Topo II) is required to separate intertwined sister chromatids before chromosome segregation can occur in mitosis. However, it remains to be resolved whether Topo II has any role in checkpoint control. Here we report that when phosphorylated, Ser 1524 of Topo IIalpha acts as a binding site for the BR...
journal_title:Nature cell biology
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doi:10.1038/s41556-019-0381-7
更新日期:2019-10-01 00:00:00
abstract::The mitochondrial inner membrane is the central energy-converting membrane of eukaryotic cells. The electrochemical proton gradient generated by the respiratory chain drives the ATP synthase. To maintain this proton-motive force, the inner membrane forms a tight barrier and strictly controls the translocation of ions....
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb1635
更新日期:2007-10-01 00:00:00
abstract::Transforming growth factor-beta (TGF-beta) induces epithelial-mesenchymal transdifferentiation (EMT) accompanied by cellular differentiation and migration. Despite extensive transcriptomic profiling, the identification of TGF-beta-inducible, EMT-specific genes has met with limited success. Here we identify a post-tran...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb2029
更新日期:2010-03-01 00:00:00
abstract::Integrin-containing focal adhesions transmit extracellular signals across the plasma membrane to modulate cell adhesion, signalling and survival. Although integrins are known to undergo continuous endo/exocytic traffic, the potential impact of endocytic traffic on integrin-induced signals is unknown. Here, we demonstr...
journal_title:Nature cell biology
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更新日期:2015-11-01 00:00:00
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更新日期:2013-07-01 00:00:00
abstract::Different sites of plasma membrane attachment may underlie functional differences between isoforms of Ras. Here we show that palmitoylation and farnesylation targets H-ras to lipid rafts and caveolae, but that the interaction of H-ras with these membrane subdomains is dynamic. GTP-loading redistributes H-ras from raft...
journal_title:Nature cell biology
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doi:10.1038/35070050
更新日期:2001-04-01 00:00:00
abstract::Mouse embryos with a loss-of-function mutation in the gene encoding the receptor tyrosine kinase ErbB4 exhibit misprojections of cranial sensory ganglion afferent axons. Here we analyse ErbB4-deficient mice, and find that morphological differences between wild-type and mutant cranial ganglia correlate with aberrant mi...
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abstract::The double fertilization process in angiosperms is based on the delivery of a pair of sperm cells by the pollen tube (the male gametophyte), which elongates towards an embryo sac (the female gametophyte) enclosing an egg and a central cell. Several studies have described the mechanisms of gametophyte interaction, and ...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb1345
更新日期:2006-01-01 00:00:00
abstract::Work over the past two years has led to a breakthrough in our understanding of the molecular basis of the directionality of the kinesin motor proteins. This breakthrough has come first from the reversal of directionality of the kinesin-related motor Ncd, followed closely by the reversal of kinesin's directionality and...
journal_title:Nature cell biology
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更新日期:1999-10-01 00:00:00
abstract::Nitric oxide (NO) is a pleiotropic signalling molecule that binds to cytochrome c oxidase (complex IV) reversibly and in competition with oxygen. This action of NO has both physiological and pathophysiological consequences. Here we report that endogenously generated NO, which disrupts the respiratory chain, may cause ...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb1188
更新日期:2004-11-01 00:00:00
abstract::In the version of this Article originally published, ref. 52 was incorrectly only attributed to its corresponding author, Fre, S., and an older title was used. The correct citation should have been: Lilja, A. M. et al. Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain...
journal_title:Nature cell biology
pub_type: 已发布勘误
doi:10.1038/s41556-018-0164-6
更新日期:2018-09-01 00:00:00
abstract::Rho GTPases are central regulators of the cytoskeleton and, in humans, are controlled by 145 multidomain guanine nucleotide exchange factors (RhoGEFs) and GTPase-activating proteins (RhoGAPs). How Rho signalling patterns are established in dynamic cell spaces to control cellular morphogenesis is unclear. Through a fam...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/s41556-020-0488-x
更新日期:2020-04-01 00:00:00
abstract::MAPKAP kinase 2 (MK2) is one of several kinases that are regulated through direct phosphorylation by p38 MAP kinase. By introducing a targeted mutation into the mouse MK2 gene, we have determined the physiological function of MK2 in vivo. Mice that lack MK2 show increased stress resistance and survive LPS-induced endo...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/10061
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abstract::The actin cytoskeleton has been implicated in restricting diffusion of plasma membrane components. Here, simultaneous observations of quantum dot-labelled FcepsilonRI motion and GFP-tagged actin dynamics provide direct evidence that actin filament bundles define micron-sized domains that confine mobile receptors. Dyna...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb1755
更新日期:2008-08-01 00:00:00
abstract::Filament-forming cytoskeletal proteins are essential for the structure and organization of all cells. Bacterial homologues of the major eukaryotic cytoskeletal families have now been discovered, but studies suggest that yet more remain to be identified. We demonstrate that the metabolic enzyme CTP synthase (CtpS) form...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb2087
更新日期:2010-08-01 00:00:00
abstract::During mammalian development, neuroepithelial cells function as mitotic progenitors, which self-renew and generate neurons. Although spindle orientation is important for such polarized cells to undergo symmetric or asymmetric divisions, its role in mammalian neurogenesis remains unclear. Here we show that control of s...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb1673
更新日期:2008-01-01 00:00:00
abstract::Collective cell migration is essential for both physiological and pathological processes. Adherens junctions (AJs) maintain the integrity of the migrating cell group and promote cell coordination while allowing cellular rearrangements. Here, we show that AJs undergo a continuous treadmilling along the lateral sides of...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb2985
更新日期:2014-07-01 00:00:00
abstract::N-WASP is a major cytoskeletal regulator that stimulates Arp2/3-mediated actin nucleation. Here, we identify a nucleation-independent pathway by which N-WASP regulates the cytoskeleton and junctional integrity at the epithelial zonula adherens. N-WASP is a junctional protein whose depletion decreased junctional F-acti...
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journal_title:Nature cell biology
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更新日期:2013-01-01 00:00:00
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journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb2098
更新日期:2010-10-01 00:00:00
abstract::Accurate chromosome segregation during cell division in metazoans relies on proper chromosome congression at the equator. Chromosome congression is achieved after bi-orientation to both spindle poles shortly after nuclear envelope breakdown, or by the coordinated action of motor proteins that slide misaligned chromoso...
journal_title:Nature cell biology
pub_type: 杂志文章
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更新日期:2014-12-01 00:00:00
abstract::The actin cable is a supracellular structure that embryonic epithelia produce to close gaps. However, the action of the cable remains debated. Here, we address the function of the cable using Drosophila dorsal closure, a paradigm to understand wound healing. First, we show that the actin cytoskeleton protein Zasp52 is...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb3421
更新日期:2016-11-01 00:00:00
abstract::Wiskott-Aldrich syndrome protein (WASP) and N-WASP have emerged as key proteins connecting signalling cascades to actin polymerization. Here we show that the amino-terminal WH1 domain, and not the polyproline-rich region, of N-WASP is responsible for its recruitment to sites of actin polymerization during Cdc42-indepe...
journal_title:Nature cell biology
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abstract::Formins have been implicated in the regulation of cytoskeletal structure in animals and fungi. Here we show that the formins Bni1 and Bnr1 of budding yeast stimulate the assembly of actin filaments that function as precursors to tropomyosin-stabilized cables that direct polarized cell growth. With loss of formin funct...
journal_title:Nature cell biology
pub_type: 杂志文章
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更新日期:2002-01-01 00:00:00
abstract::The heterogeneity of exosomal populations has hindered our understanding of their biogenesis, molecular composition, biodistribution and functions. By employing asymmetric flow field-flow fractionation (AF4), we identified two exosome subpopulations (large exosome vesicles, Exo-L, 90-120 nm; small exosome vesicles, Ex...
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journal_title:Nature cell biology
pub_type: 杂志文章
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更新日期:2011-01-01 00:00:00