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Table of Contents for this page:

  • Current Issue
  • Advanced Online Publications Articles

  • Current Issue of Nature Structural and Molecular Biology

    Nature Structural aamp; Molecular Biology - Issue - science feeds

  • Delivering nonidentical twins

  • Two sibling DNA polymerases synthesize most of the eukaryotic nuclear genome. A new study provides insights into the distinct protein interactions that deliver these replicases for asymmetric leading- and lagging-strand replication and reveals possible cross-talk between DNA replication and other cellular processes.

  • Histones push the envelope

  • The development of new strategies to deplete maternal histone proteins in vivo and in vitro has led to the discovery of unexpected roles of histones in forming a functional nuclear envelope.

  • Expanding the RNA-recognition code of PUF proteins

  • Classical PUF proteins bind to single-stranded RNA with sequence specificity that can be engineered by site-directed mutagenesis according to a simple RNA-recognition code. Now in-depth probing of the PUF RNA-recognition code enhances future design of PUF proteins and exposes hidden complexity in generating specificity.

  • SET-ting the stage for DNA repair

  • Mechanisms of DNA damage repair within actively transcribed genes are poorly understood. Five new reports shed light on the contributions of chromatin to this process by uncovering roles for histone H3 Lys36 methylation, a post-translational modification previously linked to transcription elongation, in the control of DNA-damage signaling and double strand break repair.

  • Structural basis for activity of highly efficient RNA mimics of green fluorescent protein

  • Structural elucidation of the RNA aptamer 'Spinach' reveals that a new G-quadruplex structure forms the fluorophore-binding site that confers the ability of the RNA to function as a GFP mimic.

  • Mechanism of asymmetric polymerase assembly at the eukaryotic replication fork

  • Eukaryotic DNA replication is carried out by two DNA polymerases, Polɛ and Pol δ. An in vitro–replication system reconstituted with purified yeast components identifies the factors that selectively recruit each polymerase for leading- or lagging-strand synthesis.

  • Structural basis for RNA recognition in roquin-mediated post-transcriptional gene regulation

  • Roquin controls T-cell activity through interactions with mRNAs of stimulatory receptors. Structural and functional elucidation of its RNA-binding domain reveals how it interacts with constitutive decay elements in the 3' UTR of its targets to regulate their expression.

  • The ROQ domain of Roquin recognizes mRNA constitutive-decay element and double-stranded RNA

  • Roquin recognizes the CDE element in mRNAs to promote their decay. Crystal structures of human Roquin ROQ domain in complex with RNA reveals two distinct RNA-binding sites for stem-loop RNA and dsRNA.

  • RPRD1A and RPRD1B are human RNA polymerase II C-terminal domain scaffolds for Ser5 dephosphorylation

  • Mammalian RPRD proteins bind the phosphorylated CTD of RNA pol II with different affinities. Structural elucidation and characterization of their CTD interaction domains reveal the basis of RPRD binding preferences and a role in directing CTD dephosphorylation.

  • Molecular basis for unidirectional scaffold switching of human Plk4 in centriole biogenesis

  • Plk4 regulates centriole duplication. Two centrosomal scaffold proteins, Cep192 and Cep152, are shown to interact with Plk4 in a temporally and spatially regulated manner, and structural analyses reveal that these interactions are mutually exclusive.

  • Allosteric enhancement of MAP kinase p38α's activity and substrate selectivity by docking interactions

  • MAP kinases recognize pathway-specific substrates via docking interactions. NMR analyses now reveal that docking interactions also stimulate ATP binding and phosphotransfer activity of p38α via an allosteric mechanism.

  • Identification of genes in toxicity pathways of trinucleotide-repeat RNA in C. elegans

  • A screen identifies 15 genes that modulate CUG-repeat toxicity in C. elegans, including those encoding RNA-export and clearance factors. Toxic RNAs are recognized by the NMD pathway via their 3' UTR GC content.

  • Structure of the mammalian 80S initiation complex with initiation factor 5B on HCV-IRES RNA

  • Eukaryotic initiation factor 5b (eIF5B) is essential for translation initiation. Spahn and colleagues now report cryo-EM structures of the mammalian 80S initiation complex associated with eIF5B that redefine eIF5B as a tRNA reorientation factor.

  • Selectivity mechanism of a bacterial homolog of the human drug-peptide transporters PepT1 and PepT2

  • Guettou et al. describe structural studies on a bacterial homolog of PepT1 and PepT2 peptide transporters—nutrient transporters responsible for all peptide transport across the plasma membrane—in complex with three di- or tripeptides. The data suggest how the transporter's broad peptide specificity is achieved.

  • A protein-RNA specificity code enables targeted activation of an endogenous human transcript

  • A randomized RNA library is used to determine the specificities of RNA recognition by PUF repeats. The code is then used to design a protein that targets endogenous human cyclin B1 mRNA and activates its translation.

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    Nature -Advance Online Publications

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    Nature Structural aamp; Molecular Biology - AOP - science feeds

  • TRIM28 regulates RNA polymerase II promoter-proximal pausing and pause release

  • The protein TRIM28 is identified as a factor that modulates RNA polymerase II pausing and transcriptional elongation at a large number of mammalian genes. This function is regulated by transcription-coupled phosphorylation of TRIM28 at Ser824.

  • Structure of cohesin subcomplex pinpoints direct shugoshin-Wapl antagonism in centromeric cohesion

  • The crystal structure of a human cohesin subcomplex, SA2–Scc1, guides mutagenesis analyses to dissect the antagonistic roles of shugoshin and Wapl in regulating centromeric functions during mitosis.

  • High-temporal-resolution view of transcription and chromatin states across distinct metabolic states in budding yeast

  • Analyses of transcription and chromatin states during the yeast metabolic cycle reveal the links between different chromatin modifications and gene expression. The data also show that chromatin-modifier occupancies do not precisely match modification patterns.

  • NuRD–ZNF827 recruitment to telomeres creates a molecular scaffold for homologous recombination

  • Cancer cells lacking telomerase maintain telomere lengths required for cell growth through a recombination mechanism called ALT. Now, ALT-specific nuclear receptors are shown to recruit a zinc-finger protein that directs the nucleosome remodeler and histone deacetylase NuRD to telomeres to enhance homologous recombination.

  • Structures of CRISPR Cas3 offer mechanistic insights into Cascade-activated DNA unwinding and degradation

  • Type I CRISPR-Cas systems require a target-searching Cascade complex and the Cas3 degradation machine to drive prokaryotic adaptation to alien nucleic acids. Cas3 crystal structures now reveal the mechanism of concerted DNA unwinding and degradation.

  • Architecture of the Saccharomyces cerevisiae RNA polymerase I Core Factor complex

  • Chemical cross-linking MS and supporting biochemical and genetic analyses reveal the architecture of the yeast Core Factor complex and suggest how it directs transcription of RNA Pol I at rDNA promoters.

  • RBFOX and SUP-12 sandwich a G base to cooperatively regulate tissue-specific splicing

  • Alternative pre-mRNA splicing is often jointly controlled by multiple splicing factors. Here Muto and colleagues elucidate the structural basis for cooperative RNA recognition by two splicing regulators required for tissue-specific expression of C. elegans FGFR.

  • A proton wire to couple aminoacyl-tRNA accommodation and peptide-bond formation on the ribosome

  • High-resolution structures of the 70S ribosome from Thermus thermophilus reveal a network of ordered waters in the peptidyl transferase center that suggests a mechanism for proton movement and formation and breakdown of the tetrahedral intermediate.

  • Structure of the human Cereblon–DDB1–lenalidomide complex reveals basis for responsiveness to thalidomide analogs

  • The protein Cereblon, part of an ubiquitin E3 ligase complex, is the target for anticancer thalidomide analogs. The crystal structure of human Cereblon-DDB1 with bound lenalidomide reveals how the drug affects E3 substrate recruitment.

  • RNA polymerase pausing and nascent-RNA structure formation are linked through clamp-domain movement

  • A combination of fluorescence and cross-linking assays are used to elucidate the reciprocal effects of RNA polymerase pausing and the secondary structure of the nascent transcript as it emerges from the translocating enzyme's RNA-exit channel.

  • EF-G catalyzes tRNA translocation by disrupting interactions between decoding center and codon–anticodon duplex

  • EF-G catalyzes translocation of tRNA–mRNA in the ribosome. Biochemical and structural analyses of EF-G indicate that EF-G disrupts interactions between the decoding center and the codon–anticodon duplex that constitute the barrier for translocation.

  • Structure of Nipah virus unassembled nucleoprotein in complex with its viral chaperone

  • Replication of Nipah virus, which causes human encephalitis, requires delivery of viral nucleoprotein N to the viral genome by phosphoprotein chaperone, P. The crystal structure of the N0–P core complex now reveals how the chaperone prevents premature N assembly on RNA and identifies a potential target for antiviral drugs.

  • Regulation of microRNA-mediated gene silencing by microRNA precursors

  • The precursor for miRNA-151 is found to compete with mature forms for target sites on E2f6 mRNA but not on a different mRNA. These findings indicate that miRNA processing can affect individual mRNA targets differently.

  • Asymmetric mRNA localization contributes to fidelity and sensitivity of spatially localized systems

  • A systematic analysis reveals features of proteins synthesized at distal locations owing to mRNA localization, including the presence of intrinsically disordered segments and assembly-promoting modules. These findings suggest that asymmetric protein distribution enhances interaction fidelity.

  • Delivering nonidentical twins

  • Two sibling DNA polymerases synthesize most of the eukaryotic nuclear genome. A new study provides insights into the distinct protein interactions that deliver these replicases for asymmetric leading- and lagging-strand replication and reveals possible cross-talk between DNA replication and other cellular processes.
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