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Editorial

Obama versus McCain on science and education pp999 - 1000

doi:10.1038/nsmb1008-999

A comparison of the candidates' positions on issues related to science and education points to some clear differences.


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News and Views

Competing to destroy: a fight between two RNA-degradation systems pp1001 - 1002

Geneviève Thon

doi:10.1038/nsmb1008-1001

The Argonaute-1 (Ago1) protein bound to small interfering RNAs (siRNAs) directs heterochromatin formation in fission yeast. A high-throughput sequencing approach reveals that the composition of the Ago1-bound siRNA population is sensitive to the noncanonical poly(A) polymerase Cid14, indicating that the RNA-interference and Cid14-TRAMP RNA-degradation pathways compete for substrates in fission yeast.

See also: Article by Bühler et al.


Reading and writing DNA methylation pp1003 - 1004

Albert Jeltsch

doi:10.1038/nsmb1008-1003

By recruiting the Dnmt1 DNA methyltransferase to hemimethylated DNA, the ubiquitin-like with PHD and ring finger domains 1 (UHRF1) protein plays an important part in DNA methylation. The structures of the SRA domain of UHRF1 in complex with hemimethylated DNA show that the methylated cytosine is flipped out of the DNA helix, as observed previously with DNA methyltransferases.


Sinister symphony in e1a p1005

Sabbi Lall

doi:10.1038/nsmb1008-1005


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Research Highlights

Research highlights p1006

Inês Chen, Boyana Konforti, Sabbi Lall & Michelle Montoya

doi:10.1038/nsmb1008-1006


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Perspective

Toward a more complete view of tRNA biology pp1007 - 1014

Richard Giegé

doi:10.1038/nsmb.1498


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Articles

TRAMP-mediated RNA surveillance prevents spurious entry of RNAs into the Schizosaccharomyces pombe siRNA pathway pp1015 - 1023

Marc Bühler, Noah Spies, David P Bartel & Danesh Moazed

doi:10.1038/nsmb.1481

Mutation of Cid14, a key enzyme in the TRAMP RNA surveillance pathway, has previously been shown to decrease small interfering RNA production in Schizosaccharomyces pombe. Analysis of Argonaute-associated proteins now indicates that, in the absence of Cid14, RNAs usually processed by TRAMP now enter the small interfering RNA pathway, suggesting that the RNA surveillance pathway prevents abundant RNAs from entering the RNA interference pathway.

See also: News and Views by Thon


The postfusion structure of baculovirus gp64 supports a unified view of viral fusion machines pp1024 - 1030

Jan Kadlec, Silvia Loureiro, Nicola G A Abrescia, David I Stuart & Ian M Jones

doi:10.1038/nsmb.1484

Viral fusion proteins are required for the fusion of viral and host membranes for all enveloped viruses. The structure of the Baculovirus postfusion form of glycoprotein gp64, a class III fusion protein, explains its ability to fuse with many different cell types, and structural comparisons suggest that all three classes of fusion proteins may be more closely related than previously thought.


Plasticity of the PAS domain and a potential role for signal transduction in the histidine kinase DcuS pp1031 - 1039

Manuel Etzkorn, Holger Kneuper, Pia Dünnwald, Vinesh Vijayan, Jens Krämer, Christian Griesinger, Stefan Becker, Gottfried Unden & Marc Baldus

doi:10.1038/nsmb.1493

DcuS is a multidomain membrane sensor kinase important for Escherichia coli interactions with its environment. A new approach combining solution- and solid-state NMR with in silico modeling and mutagenesis has provided a three-dimensional model for most of this large membrane protein and suggests a mechanism for DcuS activation.


Phosphorylation switches the general splicing repressor SRp38 to a sequence-specific activator pp1040 - 1048

Ying Feng, Mo Chen & James L Manley

doi:10.1038/nsmb.1485

SRp38, unlike other SR proteins, functions as a general splicing repressor when it is dephosphorylated. When phosphorylated it functions as a sequence-specific splicing activator and also affects the selection of mutually exclusive exons in the GluR-B pre-mRNA. Thus, SRp38 is a previously uncharacterized kind of splicing factor that can switch from a repressor to an activator and regulator of alternative splicing.


Cell-cycle coordination between DNA replication and recombination revealed by a vertebrate N-end rule degron-Rad51 pp1049 - 1058

Xinyi Su, Juan A Bernal & Ashok R Venkitaraman

doi:10.1038/nsmb.1490

Rad51 is an essential protein with a central role in homologous recombination. An N-end rule degron Rad51 is now used in DT-40 cells to show that Rad51 is not required for DNA synthesis, but it is necessary to resolve RPA-bound DNA structures during G2.


Hypermutation by intersegmental transfer of APOBEC3G cytidine deaminase pp1059 - 1066

Roni Nowarski, Elena Britan-Rosich, Tamar Shiloach & Moshe Kotler

doi:10.1038/nsmb.1495

APOBEC3G is a cytidine deaminase that can be incorporated into HIV-1 virions and process the viral genome upon cell infection, leading to viral hypermutation and inactivation. APOBEC3G's activities are counteracted by viral protein Vif. Using a sensitive enzymatic assay, low levels of APOBEC3G can be detected associated to Vif(+) virions. Furthermore, the authors show that APOBEC3G functions in a distributive manner and causes dispersed hypermutation via intersegmental transfer.


Structural model for strain-dependent microtubule activation of Mg-ADP release from kinesin pp1067 - 1075

Ryo Nitta, Yasushi Okada & Nobutaka Hirokawa

doi:10.1038/nsmb.1487

The binding of kinesin to microtubules promotes nucleotide exchange by the kinesin. Structural studies of the intermediate states of nucleotide exchange reveal the sequence of interactions and conformational changes that occur and the role of Mg2+ in the process, providing a testable model for microtubule-activated ADP release.


Crystal structures of the SAM-III/SMK riboswitch reveal the SAM-dependent translation inhibition mechanism pp1076 - 1083

Changrui Lu, Angela M Smith, Ryan T Fuchs, Fang Ding, Kanagalaghatta Rajashankar, Tina M Henkin & Ailong Ke

doi:10.1038/nsmb.1494

S-adenosyl-L-methionine is a methyl donor in many biological reactions and in bacteria regulates gene expression through binding to the SAM riboswitch. The structure of a third class of SAM riboswitches now indicates which features of SAM the riboswitches have converged on to distinguish it from the closely related S-adenosyl-L-homocysteine.


Mapping a molecular link between allosteric inhibition and activation of the glycine receptor pp1084 - 1093

Paul S Miller, Maya Topf & Trevor G Smart

doi:10.1038/nsmb.1492

Glycine receptors (GlyR), part of the Cys-loop neurotransmitter receptor family, are Zn2+-modulated ion channels. Electrophysiological studies on GlyR mutants indicate that the hydrophobic cores of the channel's ligand binding domains are important for allosteric communication between the ligand-binding and Zn2+-inhibitory sites. The findings suggest a general activation mechanism for this receptor family.


Inhibition of CED-3 zymogen activation and apoptosis in Caenorhabditis elegans by caspase homolog CSP-3 pp1094 - 1101

Xin Geng, Yong Shi, Akihisa Nakagawa, Sawako Yoshina, Shohei Mitani, Yigong Shi & Ding Xue

doi:10.1038/nsmb.1488

Caspases are cysteine proteases that have a central role in triggering apoptosis; thus, it is essential to tightly control their activity. Now a caspase inhibitor has been identified in Caenorhabditis elegans: CSP-3 is a caspase homolog that associates with the CED-3 zymogen, inhibiting its autoactivation.


Mal3, the Schizosaccharomyces pombe homolog of EB1, changes the microtubule lattice pp1102 - 1108

Amédée des Georges, Miho Katsuki, Douglas R Drummond, Michael Osei, Robert A Cross & Linda A Amos

doi:10.1038/nsmb.1482

In vitro, pure tubulin assembles into B-lattice microtubules, in which lateral alphaalpha and betabeta contacts between tubulin heterodimers predominate. Mal3, a homolog of the plus end–tracking protein EB1, is now shown to promote microtubule assembly into an A-lattice arrangement, forcing reconsideration of in vivo microtubule structure.


Activation of tyrosine kinases by mutation of the gatekeeper threonine pp1109 - 1118

Mohammad Azam, Markus A Seeliger, Nathanael S Gray, John Kuriyan & George Q Daley

doi:10.1038/nsmb.1486

Substitution of the active site gatekeeper residue in the BCR-ABL oncoprotein and related kinases is a common mechanism of imanitib resistance but has also been observed in drug-naïve patients. New work suggests that this residue stabilizes a hydrophobic spine that links the N and C kinase lobes, promoting the active conformation, and that adverse mutations at the gatekeeper residue further stabilize the spine. Disruption of the spine would be an attractive new goal in drug development.


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Brief Communications

A torque component present in mitotic kinesin Eg5 revealed by three-dimensional tracking pp1119 - 1121

Junichiro Yajima, Kana Mizutani & Takayuki Nishizaka

doi:10.1038/nsmb.1491

Kinesins are molecular motors that slide along microtubules. A quantum dot is now attached to a microtubule, allowing the visualization of its rotation as it is moved by kinesins. The rotational pitch provides information about the motor, revealing the low processivity of human mitotic kinesin Eg5.


The effect of H3K79 dimethylation and H4K20 trimethylation on nucleosome and chromatin structure pp1122 - 1124

Xu Lu, Matthew D Simon, Jayanth V Chodaparambil, Jeffrey C Hansen, Kevan M Shokat & Karolin Luger

doi:10.1038/nsmb.1489

Histone methylation has important consequences for chromatin activity. Now, histones with methyllysine analogs are used to reconstitute nucleosomes: the crystal structures show no global changes in nucleosomes with H3K79me2 and H4K20me3, but the latter modification enhances compaction of nucleosomal arrays.


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Addendum

Addendum: Heme is involved in microRNA processing p1125

Michael Faller, Michio Matsunaga, Sheng Yin, Joseph A Loo & Feng Guo

doi:10.1038/nsmb1008.1125


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