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Volume 16 Issue 9, September 2009

By comparing exon-intron position in higher eukaryotes to available large scale nucleosome positioning datasets, two independent groups now find that exons tend to have higher nucleosome occupancy than introns. Artwork by Erin Boyle in the style of Joan Miró, suggested by Luisa Lente. pp 990–995 and pp 996–1001, News and Views p 902

Editorial

  • Manuscript peer reviewing is at the heart of the scientific system, but it seems that these duties are often not properly (if at all) recognized by universities, funding agencies or even the rest of the scientific community.

    Editorial

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News & Views

  • The adequate and on-time response of cellular transcription to internal needs and external stimuli is a delicate task. Is the transcriptional regulator p53 on call to permit rapid activation of its target genes? A new study reports interplay of p53 with a previously unidentified regulator, calcineurin-binding protein 1 (Cabin1), and provides evidence for such a mechanism.

    • Genrich V Tolstonog
    • Wolfgang Deppert
    News & Views
  • Using bioinformatics analysis of previously published global genome deep-sequencing data, two papers now show that DNA sequences associated with nucleosomes are preferentially located in exons. The correlation between nucleosome distribution and the exon-intron organization of genes may have a key role in exon recognition at the pre-mRNA level during co-transcriptional splicing, consistent with previous findings indicating chromatin-mediated regulation of alternative splicing.

    • Alberto R Kornblihtt
    • Ignacio E Schor
    • Benjamin J Blencowe
    News & Views
  • Macrodomains function as binding modules for metabolites of NAD+, including poly(ADP-ribose). Three new studies explore how binding of poly(ADP-ribose) by the macrodomains of histone variant macroH2A1.1 and the ATP-dependent chromatin-remodeling protein ALC1 (also called CHD1L) leads to the modulation of chromatin structure, regulating nuclear functions such as DNA-damage detection and repair.

    • W Lee Kraus
    News & Views
  • An important aspect of eukaryotic gene expression is the efficient integration of transcription, pre-mRNA processing and nuclear export. A new study demonstrates that pre-mRNA transcript continuity is an essential component for maintaining productive coupling of transcription and RNA processing events.

    • Yvonne Klaue
    • Klemens J Hertel
    News & Views
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Research Highlights

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Article

  • The tumor suppressor p53 activates the transcription of a number of genes under conditions of genotoxic stress. Some of these regulated promoters show p53 occupancy even under normal conditions. Now calcineurin-binding protein 1 (Cabin1) is shown to keep p53 inactive in these promoters.

    • Hyonchol Jang
    • Soo-Youn Choi
    • Hong-Duk Youn
    Article
  • Co-transcriptional splicing of pre-mRNAs has been proposed to involve exon tethering to the elongating RNA polymerase II. By inserting a fast-cleaving ribozyme in the nascent transcript, the linear integrity of the transcript is found to be key to splicing, arguing against tethering and for a pathway that clears such disrupted transcripts.

    • Nova Fong
    • Marie Öhman
    • David L Bentley
    Article
  • Poly-ADP-ribosylation is a post-translational modification catalyzed by enzymes such as PARP1, which responds to metabolic and genotoxic stress. Now macrodomain-containing proteins are shown to rapidly move to PARP1 activation sites, and recruitment of the macrodomain-containing histone macroH2A1.1 results in local chromatin changes.

    • Gyula Timinszky
    • Susanne Till
    • Andreas G Ladurner
    Article
  • The cap binding complex (CBC) interacts with mRNAs and snRNAs and accompanies them to the cytoplasm, where they are released and CBC is imported back into the nucleus by the importin complex. Multiple approaches are now combined to gain structural and functional insights into the regulation and coordination of these CBC interactions.

    • Sandra M G Dias
    • Kristin F Wilson
    • Richard A Cerione
    Article
  • Nucleosomes can interfere with DNA binding by factors, but previous work showed that protein-binding sites on a single nucleosome are accessible. Dynamics in the context of higher-order chromatin structure are now examined, with compaction dynamics and DNA-binding site exposure on a centrally placed nucleosome in an array assessed.

    • Michael G Poirier
    • Eugene Oh
    • Jonathan Widom
    Article
  • Phosphorylation-dependent SUMOylation of MEF2A promotes postsynaptic dendrite differentiation. Analyses now reveal that a surface on the SUMO E2 UBC9 is responsible for integrating phosphorylation signal recognition and SUMOylation and suggests that regulation of some SUMO substrate recognition events may have evolved to use the E2 rather than an E3 ligase.

    • Firaz Mohideen
    • Allan D Capili
    • Christopher D Lima
    Article
  • miRNAs are loaded onto Argonautes (Agos) to guide silencing of targets, but duplex unwinding is required for targeting. Detection of Drosophila Ago1 complexes containing the duplexed or unwound miRNA now give insight into the basis for cleavage-independent unwinding of miRNA duplexes to generate a functional, mature complex.

    • Tomoko Kawamata
    • Hervé Seitz
    • Yukihide Tomari
    Article
  • Platelets are anucleate elements in the cardiovascular system involved in clotting. Platelets are now found to contain microRNAs and the key cytoplasmic elements of a processing and effector pathway, suggesting that platelet mRNAs may be subjected to microRNA regulation.

    • Patricia Landry
    • Isabelle Plante
    • Patrick Provost
    Article
  • X family DNA polymerases can fill short DNA gaps by binding both the 5′ and 3′ ends of the gap. What happens to the template strand is now revealed in the crystal structure of human polymerase λ bound to a 2-nucleotide gap substrate. The template strand is scrunched, with the additional base in an extrahelical position going into an enzyme pocket.

    • Miguel Garcia-Diaz
    • Katarzyna Bebenek
    • Thomas A Kunkel
    Article
  • Prions can adopt a transmissible β-sheet-rich conformation and also form strains with different structural and biological properties. Polymorphic crystal structures of peptides from prion- and other amyloid-forming proteins suggest the structural basis for prion strains, revealing two potential mechanisms: packing and segmental polymorphism.

    • Jed J W Wiltzius
    • Meytal Landau
    • David Eisenberg
    Article
  • DNA polymerase δ (Pol δ) has a crucial role in eukaryotic replication. Now the crystal structure of the yeast DNA Pol δ catalytic subunit in complex with template primer and incoming nucleotide is presented at 2.0-Å resolution, providing insight into its high fidelity and a framework to understand the effects of mutations involved in tumorigenesis.

    • Michael K Swan
    • Robert E Johnson
    • Aneel K Aggarwal
    Article
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Brief Communication

  • The anaphase promoting complex (APC) is a key cell-cycle regulator that has ubiquitin-ligase activity. The first structure of a complex formed between APC subunits, that of CDC26 and APC6, provides detailed structural information of APC components and suggests how CDC26 may stabilize APC6 and other complex subunits.

    • Jing Wang
    • Billy T Dye
    • Brenda A Schulman
    Brief Communication
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Analysis

  • Splicing and transcription have been argued to be coupled, but the mechanisms behind this are unclear. Published data sets examining nucleosome positioning are now analyzed and show that exons tend to have higher nucleosome occupancy than introns. This may indicate why metazoan exons are 150 nucleotides, similar to the length of DNA on a nucleosome.

    • Schraga Schwartz
    • Eran Meshorer
    • Gil Ast
    Analysis
  • Chromatin influences transcription, but its effects on downstream processing have been less clear. Analyses of published high-throughput data examining nucleosomal positions in T cell and C. elegans genomes now indicates that intron-exon architecture is reflected in nucleosome occupancy.

    • Hagen Tilgner
    • Christoforos Nikolaou
    • Roderic Guigó
    Analysis
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