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  1. Gathering by the Red Sea highlights links between environment and epigenetics

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    The number of conferences on epigenetics has been increasing in the past decade, underscoring the impact of the field on a variety of areas in biology and medicine. However, the mechanistic role of the epigenome in adaptation and inheritance, and how the environment may impinge on epigenetic control, are topics of growing debate. Those themes were the focus of the inaugural international King Abdullah University of Science and Technology (KAUST) Research Conference on Environmental Epigenetics in Saudi Arabia, where more than 100 participants from 19 countries enjoyed vibrant scientific discussions and a pleasant February breeze from the Red Sea.
  2. A glimpse into chromatin remodeling

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    Chromatin remodelers are ATP-driven enzymes that can slide nucleosomes along DNA. Chen and colleagues present a tantalizing ∼4-Å view of the SWI/SNF ATPase motor bound to the nucleosome, which offers novel structural clues into the remodeling process.
  3. Distinct mechanisms obviate the potentially toxic effects of inverted-repeat Alu elements on cellular RNA metabolism

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    Two new studies show that RNA-binding proteins can mediate distinct and beneficial effects to cells by binding to the extensive double-stranded RNA (dsRNA) structures of inverted-repeat Alu elements (IRAlus). One study reports stress-induced export of the 110-kDa isoform of the adenosine deaminase acting on RNA 1 protein (ADAR1p110) to the cytoplasm, where it binds IRAlus so as to protect many mRNAs encoding anti-apoptotic proteins from degradation. The other study demonstrates that binding of the nuclear helicase DHX9 to IRAlus embedded within RNAs minimizes defects in RNA processing.

    See also: Article by Masayuki Sakurai et al.

  4. Frozen in action: cryo-EM structure of a GPCR–G-protein complex

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    Interaction with heterotrimeric G proteins is a hallmark of G-protein-coupled receptor (GPCR) family members, and it is the key step for a diverse range of cell-signaling cascades. A recent cryo-EM structure of the human calcitonin receptor (CTR) in complex with a G-protein heterotrimer reveals novel insights into receptor–G-protein coupling.
  5. Carb cutting works better with a partner

    O-GlcNAc is a reversible post-translational modification that is added by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). OGA is emerging as a therapeutic target for multiple diseases, but its structure has been elusive until now.
  6. Splicing of Ezh1 gets muscle out of stressful situations

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    As cells undergo terminal differentiation, the composition of Polycomb-repressive complex 2 (PRC2) changes and the histone H3K27 methyltransferase Ezh2 is progressively replaced by its homolog Ezh1. By identifying an enzymatically inactive splice variant of Ezh1 that is sensitive to cellular stress, Bodega et al. now demonstrate that PRC2–Ezh1 has an essential role in establishing an altered gene expression program required for postmitotic muscle cells to adapt to environmental changes.

    See also: Article by Beatrice Bodega et al.

  7. Remodelers tap into nucleosome plasticity

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    Chromatin-remodeling enzymes perform the formidable task of reorganizing the structure of a stable macromolecular assembly, the nucleosome. Recently published work demonstrates that the SNF2H chromatin remodeler distorts the histone octamer structure upon binding to the nucleosome, then taps into this induced plasticity to productively achieve nucleosome sliding.
  8. Surveillance states

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    The binding of foreign peptides to host major histocompatibility complex (MHC) forms the basis of adaptive immune recognition. The MHC and T cell receptors (TCRs) use diverse structural solutions to enhance peptide presentation and recognition, and two new reports provide insights into noncanonical modes of detection and binding.

    See also: Article by Phillip Pymm et al., Article by InYoung Song et al.

  9. Unearthing worm replication origins

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    Unlike in animals in which gastrulation marks the onset of zygotic transcription and a transition from random to site-specific localization of replication origins, transcription and origin specification in Caenorhabditis elegans are in place before gastrulation. Nonetheless, origin-site redistribution takes place after gastrulation, and is coordinated with changes in the sites of active transcription.

    See also: Article by Marta Rodríguez-Martínez et al.

  10. Mechanisms for targeted, purposeful mutation revealed in an APOBEC–DNA complex

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    Targeted deamination of cytosine bases in DNA by AID/APOBEC-family enzymes is critical for proper immune function, but it also poses risks to genomic integrity. New structures reported by Harris, Aihara and colleagues offer the first glimpses into the enzyme–DNA complex and reveal both expected and unexpected insights into the DNA-binding mode involved in targeting purposeful mutation.

    See also: Article by Ke Shi et al.

  11. The diverse roles of Hsp90 and where to find them

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    The Eighth International Conference on the Hsp90 Chaperone Machine took place in November 2016 at the Seeon Abbey in Germany. This year's program focused on a variety of topics, reflecting Hsp90's diverse roles in cellular and physiological function. The highlights included structural insights into the Hsp90 folding mechanism and conformational dynamics, post-translational modifications, client protein maturation, Hsp90 cochaperone function and Hsp90's role in disease physiology.
  12. CFTR structure: lassoing cystic fibrosis

    Loss of function of the CFTR anion channel leads to cystic fibrosis, the most common inherited condition in humans of European origin. A recently reported structure for CFTR at 3.7-Å resolution reveals an unexpected 'lasso' domain and provides new insights into channel function in healthy individuals and in people with cystic fibrosis.
  13. Functional RNA classes: a matter of time?

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    Little is known about the functions of long noncoding RNAs compared with the amount of accumulated knowledge concerning protein-mediated mechanisms. A report now proposes a novel RNA classification based on similar kinetics of RNA synthesis, processing and turnover, and the authors predict that RNAs within each class might share functional properties.

    See also: Resource by Neelanjan Mukherjee et al.

  14. New pieces to an old puzzle: identifying the warfarin-binding site that prevents clotting

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    Warfarin has been the most widely prescribed anticoagulant for decades. It functions by inhibiting the membrane enzyme vitamin K epoxide reductase (VKOR), but the molecular details of this effect have remained elusive. Two new studies shed light on the warfarin-VKOR interaction. The work has implications for precision medicine and could guide drug discovery.

    See also: Article by Guomin Shen et al., Article by Katrin J Czogalla et al.

  15. Single-virus tracking uncovers the missing link between HIV integration site location and viral gene expression

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    The site of HIV genome integration is likely a contributing factor in viral gene expression, but such context-specific effects are difficult to demonstrate at the population level. A new approach overcomes this obstacle by tracking individual, barcoded viruses to investigate the relationship between integration site location and the corresponding viral transcription, thereby providing insights essential for understanding HIV production, latency and reactivation.

    See also: Article by Heng-Chang Chen et al.

  16. Break-induced replication: an unhealthy choice for stress relief?

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    Determining the molecular mechanisms responsible for trinucleotide DNA repeat expansions is critical, as such expansions underlie many neuromuscular and neurodegenerative disorders. Mirkin and colleagues now propose that large-scale expansions of trinucleotide repeats can be generated by DNA-break-induced replication.

    See also: Article by Jane C Kim et al.

  17. Keeping time

    Daily rhythms are a constant part of life. This special Focus issue explores the molecular mechanisms that underlie the generation of circadian dynamics.
  18. The origin of oxidized guanine resolves the puzzle of oxidation-induced telomere-length alterations

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    Although oxidative stress has long been considered to be a major factor contributing to telomere shortening, recent work has established that oxidative stress and DNA damage are linked to telomere lengthening. Now, Opresko and colleagues resolve this apparent discrepancy by showing that differential modulation of telomerase activity depends on the origin of a common oxidative guanine lesion.

    See also: Article by Elise Fouquerel et al.

  19. Climbing to the peak of nascent-chain knowledge

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    During protein synthesis, the growing nascent polypeptide chain acts as a positive or negative regulator of the rate of peptide-bond formation and ribosomal fidelity, and influences the efficiency of downstream protein-folding and targeting events. At a recent international meeting held on the banks of Lake Kawaguchi in Japan, scientists and students investigating diverse aspects of nascent-chain biology met to discuss their latest findings in the scenic presence of Mount Fuji.