TABLE OF CONTENTS
| March 2012 Volume 19, Issue 3 |  | | |  |  News and Views
Research Highlights
Articles
Brief Communications
Errata
Corrigenda
| | | | | | | Advertisement |  | Focus on Membrane dynamics
The January 2012 issue of Nature Cell Biology presents a series of review articles by leading scientists on recent developments in membrane dynamics - including endocytosis, and vesicle biogenesis and transport - and the importance of these processes in development and disease.
Access the Focus online:
www.nature.com/ncb/webfocus/membranedynamics |
| | | | News and Views |  Top | |  | | A 'pivotal' new rule for microRNA-mRNA interactions pp265 - 266
Giovanni Stefani and Frank J Slack
doi:10.1038/nsmb.2256
Finding biologically relevant targets is a prerequisite for understanding the function of any trans regulator of gene expression, but this can be particularly challenging with microRNAs (miRNAs). A study in this issue addresses the problem by identifying a novel mode of miRNA target recognition.
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See also: Article by Chi et al.
| | Research Highlights | | | | HOPS from head to tail | Twist in the RNAPII tail | Inhibiting E2s | Restoring order
| Articles | | | | Structural characterization of full-length NSF and 20S particles pp268 - 275
Lei-Fu Chang, Song Chen, Cui-Cui Liu, Xijiang Pan, Jiansen Jiang, Xiao-Chen Bai, Xin Xie, Hong-Wei Wang and Sen-Fang Sui
doi:10.1038/nsmb.2237
The 20S particle, which is composed of NSF, SNAP and the SNARE complex, is important in fusion events. Single-particle cryo-EM and negative stain EM studies of the 20S particle and of NSF in its different nucleotide states suggest how nucleotide-dependent conformational changes in NSF may generate a force via ATP hydrolysis, providing insight into disassembly of SNARE by NSF.
Abstract | Full Text | PDF
| | | | DNAPKcs-dependent arrest of RNA polymerase II transcription in the presence of DNA breaks pp276 - 282
Tibor Pankotai, Céline Bonhomme, David Chen and Evi Soutoglou
doi:10.1038/nsmb.2224
DNA double-strand breaks (DSBs) can affect many cellular processes, including transcription. Now the dynamics of RNA polymerase II is studied, following the induction of a single DSB within transcribed genes in human cell lines. The results reveal that the DSB causes inhibition of transcription elongation and reinitiation, in a manner that is dependent on the activity of DNA protein kinase and the proteasome.
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| | ERK1 and ERK2 regulate embryonic stem cell self-renewal through phosphorylation of Klf4 pp283 - 290
Myoung Ok Kim, Sung-Hyun Kim, Yong-Yeon Cho, Janos Nadas, Chul-Ho Jeong, Ke Yao, Dong Joon Kim, Dong-Hoon Yu, Young-Sam Keum, Kun-Yeong Lee, Zunnan Huang, Ann M Bode and Zigang Dong
doi:10.1038/nsmb.2217
Krüppel-like factor 4 (Klf4) promotes the self-renewal of embryonic stem cells, but how Klf4 itself is regulated is unclear. ERK1 and ERK2 are now found to phosphorylate Klf4, targeting it for degradation via the ubiquitin-proteasome pathway and promoting cellular differentiation.
Abstract | Full Text | PDF
| | | | Structure and mechanism of the UvrA–UvrB DNA damage sensor pp291 - 298
Danaya Pakotiprapha, Martin Samuels, Koning Shen, Johnny H Hu and David Jeruzalmi
doi:10.1038/nsmb.2240
The bacterial nucleotide excision repair pathway starts with the sensor complex UvrA–UvrB scanning the genome and undergoing conformational change when DNA lesions are detected. Now crystal structures of a UvrA dimer and the UvrA–UvrB complex, along with biochemical analyses, provide insight into these early nucleotide excision repair events.
Abstract | Full Text | PDF
| | | | A novel actin binding site of myosin required for effective muscle contraction pp299 - 306
Boglárka H Várkuti, Zhenhui Yang, Bálint Kintses, Péter Erdélyi, Irén Bárdos-Nagy, Attila L Kovács, Péter Hári, Miklós Kellermayer, Tibor Vellai and András Málnási-Csizmadia
doi:10.1038/nsmb.2216
To maintain efficient force generation, myosins must couple the ATPase cycle with actin binding and lever movement, but the mechanism for this coupling and actin activation of myosin has remained elusive. Now, a conserved actin-binding loop is found to be responsible for activating the ATPase by acceleration of the lever swing, increasing the ratio of mechanically productive to futile actomyosin cycles.
Abstract | Full Text | PDF
| | | | Anticheckpoint pathways at telomeres in yeast pp307 - 313
Cyril Ribeyre and David Shore
doi:10.1038/nsmb.2225
How yeast telomeres avoid triggering DNA damage checkpoints is studied by creating de novo telomere ends with different amounts of telomeric repeats. Rif1 and Rif2 protect short telomere tracts through different mechanisms and by blocking the accumulation of proteins that can activate checkpoint kinase Mec1. Moreover, long telomere tracts can perturb DNA end processing on neighboring short tracts and hence dampen checkpoint activation.
Abstract | Full Text | PDF
| | | | The Elongator subcomplex Elp456 is a hexameric RecA-like ATPase pp314 - 320
Sebastian Glatt, Juliette Létoquart, Céline Faux, Nicholas M I Taylor, Bertrand Séraphin and Christoph W Müller
doi:10.1038/nsmb.2234
The Elongator complex has been associated with a wide range of cellular processes, including post-transcriptional modification of tRNAs. Structural and biochemical analyses of Elongator proteins 4, 5 and 6 now show that they form a RecA-like hexameric ring that binds tRNAs in a manner regulated by ATP hydrolysis.
Abstract | Full Text | PDF
| | | | An alternative mode of microRNA target recognition pp321 - 327
Sung Wook Chi, Gregory J Hannon and Robert B Darnell
doi:10.1038/nsmb.2230
MicroRNAs are thought to repress mRNA targets through perfect pairing with their seed region, but a sizeable number of miRNA interaction sites are orphans, without a perfect canonical miRNA partner. Now a large number of miRNAs are found to use an alternative binding mode that involves the bulging out of an unpaired mRNA nucleotide, leading to a functional mRNA-miRNA interaction.
Abstract | Full Text | PDF
See also: News and Views by Stefani & Slack
| | | | Structural basis for the assembly and nucleic acid binding of the TREX-2 transcription-export complex pp328 - 336
Andrew M Ellisdon, Lyudmila Dimitrova, Ed Hurt and Murray Stewart
doi:10.1038/nsmb.2235
The multisubunit TREX-2 complex coordinates transcription and processing of many actively transcribed nascent mRNAs with the recruitment of export factors at nuclear pores. Now the structure of the Sac3–Sem1–Thp1 complex reveals a platform that binds nucleic acids, promoting mRNA export.
Abstract | Full Text | PDF
| | | | Balanced interactions of calcineurin with AKAP79 regulate Ca2+–calcineurin–NFAT signaling pp337 - 345
Huiming Li, Matthew D Pink, Jonathan G Murphy, Alexander Stein, Mark L Dell'Acqua and Patrick G Hogan
doi:10.1038/nsmb.2238
The AKAP79 scaffold protein couples plasma membrane Ca2+ influx in neurons to activation of calcineurin, which in turn activates NFAT. Analysis of this interaction shows that AKAP79 and NFAT bind the same interface on calcineurin, but the affinity of the calcineurin-AKAP79 interaction is finely balanced to promote calcineurin recruitment to the scaffold while still allowing calcineurin release for NFAT activation.
Abstract | Full Text | PDF
| | | | Concentration-dependent control of pyruvate kinase M mutually exclusive splicing by hnRNP proteins pp346 - 354
Mo Chen, Charles J David and James L Manley
doi:10.1038/nsmb.2219
Alternative splicing of the pyruvate kinase M (PKM) pre-mRNA, resulting in the exclusion of either exon 9 or 10, requires a small set of splicing factors, hnRNPA1, hnRNPA2 and PTB. A new study reveals that these general splicing factors function through a concentration-dependent mechanism, coupled with nonsense-mediated decay, to determine the outcome of PKM pre-mRNA splicing.
Abstract | Full Text | PDF
| | Brief Communications | Top | | | | Crystal structure of an asymmetric trimer of a bacterial glutamate transporter homolog pp355 - 357
Grégory Verdon and Olga Boudker
doi:10.1038/nsmb.2233
Glutamate transporters are trimeric pumps that couple the uptake of glutamate to the transport of cations. A new crystal structure of an archaeal trimeric glutamate transporter homolog, GltPh, captured in an intermediate conformation between the outward and inward facing states, provides insights into the transport mechanism.
First paragraph | Full Text | PDF
| | | | The structural basis of transferrin sequestration by transferrin-binding protein B pp358 - 360
Charles Calmettes, Joenel Alcantara, Rong-Hua Yu, Anthony B Schryvers and Trevor F Moraes
doi:10.1038/nsmb.2251
Some bacterial pathogens can obtain iron from the human host by extracting it from transferrin via two bacterial surface proteins, TfbA and TfbB. Now the crystal structures of Neisseria meningitidis TfbB in its apo state and bound to human transferrin reveal how TfbB sequesters transferrin and initiates iron release.
First paragraph | Full Text | PDF
| | | | Methylation of H4 lysines 5, 8 and 12 by yeast Set5 calibrates chromatin stress responses pp361 - 363
Erin M Green, Gloria Mas, Nicolas L Young, Benjamin A Garcia and Or Gozani
doi:10.1038/nsmb.2252
Numerous methylated residues exist on histone tails, the functional significance of which remains unknown. New studies in budding yeast now identify monomethylation of histone H4 lysine residues 5, 8 and 12 as functionally important marks that regulate cell growth and stress responses and are catalyzed by the first known H4 methyltransferase in budding yeast, Set5.
First paragraph | Full Text | PDF
| | Errata | Top | | | | ABC ATPase signature helices in Rad50 link nucleotide state to Mre11 interface for DNA repair p364
Gareth J Williams, R Scott Williams, Jessica S Williams, Gabriel Moncalian, Andrew S Arvai, Oliver Limbo, Grant Guenther, Soumita SilDas, Michal Hammel, Paul Russell and John A Tainer
doi:10.1038/nsmb0312-364a
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| | | | Crystal structure of a monomeric retroviral protease solved by protein folding game players p364
Firas Khatib, Frank DiMaio, Seth Cooper, Maciej Kazmierczyk, Miroslaw Gilski, Szymon Krzywda, Helena Zabranska, Iva Pichova, James Thompson, Zoran Popović, Mariusz Jaskolski and David Baker
doi:10.1038/nsmb0312-364b
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| | Corrigenda | Top | | | | miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT p364
Marc R Fabian, Maja K Cieplak, Filipp Frank, Masahiro Morita, Jonathan Green, Tharan Srikumar, Bhushan Nagar, Tadashi Yamamoto, Brian Raught, Thomas F Duchaine and Nahum Sonenberg
doi:10.1038/nsmb0312-364c
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| | | | Transcriptome-wide sequencing reveals numerous APOBEC1 mRNA-editing targets in transcript 3′ UTRs p364
Brad R Rosenberg, Claire E Hamilton, Michael M Mwangi, Scott Dewell and F Nina Papavasiliou
doi:10.1038/nsmb0312-364d
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| | | | Human mitochondrial transcription factor A induces a U-turn structure in the light strand promoter p364
Anna Rubio-Cosials, Jasmin F Sidow, Nereida Jiménez-Menendez, Pablo Fernández-Millán, Julio Montoya, Howard T Jacobs, Miquel Coll, Pau Bernadó and Maria Solà
doi:10.1038/nsmb0312-364e
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