Proteins that contain a functional Z-DNA-binding domain localize to cytoplasmic stress granules

Long double-stranded RNA may undergo hyper-editing by adenosine deaminases that act on RNA (ADARs), where up to 50% of adenosine residues may be converted to inosine. However, although numerous RNAs may undergo hyper-editing, the role for inosine-containing hyper-edited double-stranded RNA in cells is poorly understood. Nevertheless, editing plays a critical role in mammalian cells, as highlighted by the analysis of ADAR-null mutants. In particular, the long form of ADAR1 (ADAR1(p150)) is essential for viability. Moreover, a number of studies have implicated ADAR1(p150) in various stress pathways. We have previously shown that ADAR1(p150) localized to cytoplasmic stress granules in HeLa cells following either oxidative or interferon-induced stress. Here, we show that the Z-DNA-binding domain (Zα(ADAR1)) exclusively found in ADAR1(p150) is required for its localization to stress granules. Moreover, we show that fusion of Zα(ADAR1) to either green fluorescent protein (GFP) or polypyrimidine binding protein 4 (PTB4) also results in their localization to stress granules. We additionally show that the Zα domain from other Z-DNA-binding proteins (ZBP1, E3L) is likewise sufficient for localization to stress granules. Finally, we show that Z-RNA or Z-DNA binding is important for stress granule localization. We have thus identified a novel role for Z-DNA-binding domains in mammalian cells

Covalent Post-assembly Modification Triggers Multiple Structural Transformations of a Tetrazine-Edged Fe4L6 Tetrahedron

Covalent post-assembly modification (PAM) reactions are useful synthetic tools for functionalizing and stabilizing self-assembled metal-organic complexes. Recently, PAM reactions have also been explored as stimuli for triggering supramolecular structural transformations. Herein we demonstrate the use of inverse electron-demand Diels-Alder (IEDDA) PAM reactions to induce supramolecular structural transformations starting from a tetrazine-edged FeII4L6 tetrahedral precursor. Following PAM, this tetrahedron rearranged to form three different architectures depending on the addition of other stimuli: an electron-rich aniline or a templating anion. By tracing the stimulus-response relationships within the system, we deciphered a network of transformations that mapped different combinations of stimuli onto specific transformation products. Given the many functions being developed for self-assembled three-dimensional architectures, this newly established ability to control the interconversion between structures using combinations of different stimulus types may serve as the basis for switching the functions expressed within a system.D.A.R. acknowledges the Gates Cambridge Trust. B.S.P. acknowledges the Royal Commission for the Exhibition of 1851 Fellowship and Corpus Christi College, Cambridge. This work was supported by the UK Engineering and Physical Sciences Research Council (EP/M01083X/1)

Tetramine Aspect Ratio and Flexibility Determine Framework Symmetry for Zn8L6 Self-Assembled Structures

We derive design principles for the assembly of rectangular tetramines into Zn8L6 pseudo-cubic coordination cages. Because of the rectangular, as opposed to square, geometry of the ligand panels, and the possibility of either Delta or ? handedness of each metal center at the eight corners of the pseudo-cube, many different cage diastereomers are possible. Each of the six tetra-aniline subcomponents investigated in this work assembled with zinc(II) and 2-formylpyridine in acetonitrile into a single Zn8L6 pseudo-cube diastereomer, however. Each product corresponded to one of four diastereomeric configurations, with T, T-h, S-6 or D-3 symmetry. The preferred diastereomer for a given tetra-aniline subcomponent was shown to be dependent on its aspect ratio and conformational flexibility. Analysis of computationally modeled individual faces or whole pseudo-cubes provided insight as to why the observed diastereomers were favored

Post-assembly Modification of Tetrazine-Edged Fe(II)4L6 Tetrahedra.

Post-assembly modification (PAM) is a powerful tool for the modular functionalization of self-assembled structures. We report a new family of tetrazine-edged Fe(II)4L6 tetrahedral cages, prepared using different aniline subcomponents, which undergo rapid and efficient PAM by inverse electron-demand Diels-Alder (IEDDA) reactions. Remarkably, the electron-donating or -withdrawing ability of the para-substituent on the aniline moiety influences the IEDDA reactivity of the tetrazine ring 11 bonds away. This effect manifests as a linear free energy relationship, quantified using the Hammett equation, between σ(para) and the rate of the IEDDA reaction. The rate of PAM can thus be adjusted by varying the aniline subcomponent.This work was supported by the UK Engineering and Physical Sciences Research Council (EPSRC). The au-thors thank Diamond Light Source (UK) for synchro-tron beamtime on I19 (MT8464), the Department of Chemistry NMR facility, University of Cambridge, and the EPSRC UK National Mass Spectrometry Facility at Swansea University. D.A.R. acknowledges the Gates Cambridge Trust for Ph.D. funding. B.S.P. acknowledges the Herchel Smith Research Fellowship from the University of Cambridge and the Fellowship from Corpus Christi College, Cambridge.This is the final version of the article. It first appeared from the American Chemical Society via http://dx.doi.org/10.1021/jacs.5b0508

Sterics and Hydrogen Bonding Control Stereochemistry and Self-Sorting in BINOL-Based Assemblies

Here we demonstrate how the hydrogen-bonding ability of a BINOL-based dialdehyde subcomponent dictated the stereochemical outcome of its subsequent self-assembly into one diastereomeric helicate form when bearing free hydroxy groups, and another in the case of its methylated congener. The presence of methyl groups also altered the self-sorting behavior when mixed with another, short linear dialdehyde subcomponent, switching the outcome of the system from narcissistic to integrative self-sorting. In all cases, the axial chirality of the BINOL building block also dictated helicate metal center handedness during stereospecific self-assembly. A new family of stereochemically pure heteroleptic helicates were thus prepared using the new knowledge gained. We also found that switching from FeII to ZnII, or the incorporation of a longer linear ligand, favored heteroleptic structure formation

Selective Anion Extraction and Recovery Using a FeII4L4 Cage

Selective anion extraction is useful for the recovery and purification of valuable chemicals, and in the removal of pollutants from the environment. Here we report that FeII4L4 cage 1 is able to extract an equimolar amount of ReO4−, a high-value anion and a nonradioactive surrogate of TcO4−, from water to nitromethane. Importantly, the extraction was efficiently performed even in the presence of 10 other common anions in water, highlighting the high selectivity of 1 for ReO4−. The extracted guest could be released into water as the cage disassembled in ethyl acetate, and then 1 could be recycled by switching the solvent to acetonitrile. The versatile solubility of the cage also enabled complete extraction of ReO4− (as the tetrabutylammonium salt) from an organic phase into water by using the sulfate salt of 1 as the extractant.This work was supported by the UK Engineering and Physical Sciences Research Council (EPSRC EP/M008258/1). The authors thank the Department of Chemistry NMR facility, University of Cambridge for performing some NMR experiments, and the EPSRC UK National Mass Spectrometry Facility at Swansea University for carrying out high resolution mass spectrometry. D. Z. acknowledges the Herchel Smith Research Fellowship from the University of Cambridge

Patterns of media coverage repeated in online abuse on high-profile criminal cases

What relationship do the mainstream media have with online abuse on high-profile criminal cases? This article hopes to make a start at answering this question by examining tweets containing the #McCann hashtag, utilised by a highly engaged community of users to comment on all matters related to the disappearance of British child Madeleine McCann. On #McCann, the child’s parents and other players are often singled out as the perpetrators of her disappearance and other crimes, in a blend of harassment, defamation and insults with conspiracy theories, disinformation and a strong anti-establishment vein typical of the posttruth era. Through an experimental digital ethnography blending elements of content and discourse analysis, this research has observed the #McCann conversation and analysed 500 tweets with the hashtag, observing that some of the most offensive theories posted by users on Twitter reprised themes seen in the mainstream media at the time of the disappearance, which resulted in defamation lawsuits by the McCanns and in complaints about unethical reporting at the Leveson Inquiry. This raises questions about the mainstream media’s responsibility and duty of care towards people they report on in the digital age, and showcases a symbiotic yet diffident relationship between anti-establishment online users and traditional news media

Post-assembly modification of kinetically metastable FeII2L3 triple helicates

We report the covalent post-assembly modification of kinetically metastable amine-bearing FeII2L3 triple helicates via acylation and azidation. Covalent modification of the metastable helicates prevented their reorganization to the thermodynamically favored FeII4L4 tetrahedral cages, thus trapping the system at the non-equilibrium helicate structure. This functionalization strategy also conveniently provides access to a higher-order tris(porphyrinatoruthenium)–helicate complex that would be difficult to prepare by de novo ligand synthesis

Anion Binding in Water Drives Structural Adaptation in an Azaphosphatrane-Functionalized Fe(II)4L4 Tetrahedron

Anion-templated aqueous self-assembly resulted in the formation of an endohedrally functionalized Fe$^\text{II}$$_{4}$L$_4$ tetrahedron from azaphosphatrane-based subcomponents. This new water-soluble cage is flexible and able to encapsulate anions with volumes ranging from 35 to 219 Å$^3$ via hydrogen bonding and electrostatic interactions. It structurally adapts in response to the size and shape of the template anions, dynamically adopting a conformation either where all four azaphosphatrane $^{+}$P-H vectors point inward, or else where one points outward and the other three inward. The two cage isomers can coexist in solution and interconvert. A shape memory phenomenon was observed during guest displacement because guest exchange occurs more rapidly than structural reconfiguration.This work was supported by the UK Engineering and Physical Sciences Research Council (EPSRC EP/M008258/1). The authors thank the Department of Chemistry NMR facility, University of Cambridge for performing some NMR experiments, and the EPSRC UK National Mass Spectrometry Facility at Swansea University for carrying out high-resolution mass spectrometry. D.Z. acknowledges a grant from the China Scholarship Council, Accueil Doc Bursary from France RhôneAlpes Region, and Enveloppe AttractivitéFellowship from ENSLyon for Ph.D. studies