Featured Articles - January 2012

Featured Articles highlight the best papers published in NAR. These articles are chosen by the Executive Editors on the recommendation of Editorial Board Members and Referees. They represent the top 5% of papers in terms of originality, significance and scientific excellence. The articles are accompanied by a brief synopsis explaining the findings of the paper and where they fit in the broader context of nucleic acids research.

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Quantitative prediction of 3D solution shape and flexibility of nucleic acid nanostructures
Do-Nyun Kim, Fabian Kilchherr, Hendrik Dietz, and Mark Bathe

Nucleic acids can be programmed to self-assemble into complex nanometer-scale shapes for diverse applications in the biomolecular and materials sciences. As in any design and manufacturing process, key to success is the ability to meet target design criteria with high fidelity and low cost. Here the authors present and validate experimentally a computational technology that quantitatively predicts two of the most important design criteria of nucleic acid nanostructures: 3D solution shape and flexibility. This technology, which is available as an online resource, provides designers with rapid feedback on their nucleic acid design to eliminate the costly and time-consuming design-synthesize-validate process performed currently. Read on

Stringency of start codon selection modulates autoregulation of translation initiation factor eIF5
Gary Loughran, Matthew S. Sachs, John F. Atkins, and Ivaylo P. Ivanov

Gene regulation exploiting variations in the stringency of start codon selection in eukaryotes was discovered only recently. In fact until 3 years ago it was assumed that stringency is invariable in eukaryotes and the only determinate for utilization of a given start codon is its initiation context. In this paper demonstrates that the protein levels of eIF1 and eIF5 and the balance between the two are major determinants of stringency of start codon selection in human cells. The data also suggests that eIF1 and eIF5 genes are components of a binary autoregulatory system evolved to stabilize the levels of stringency of start codon selection. Read on

Structuring the bacterial genome: Y1-transposases associated with REP-BIME sequences
Bao Ton-Hoang, Patricia Siguier, Yves Quentin, Séverine Onillon, Brigitte Marty, Gwennaele Fichant, and Mick Chandler

Bacterial REPs, highly repeated sequences found in intergenic regions, play a variety of key roles in host physiology. Although identified 30 years ago, it is not known how REPs have spread throughout the host genomes. A group of recently identified REP-associated proteins, TnpAREP has been proposed to be responsible for REP amplification. TnpAREP are closely related to transposases encoded by a new family of bacterial IS which use single strand transposition. To address the role of TnpAREP in REP evolution, we analyse their distribution and show that in vitro TnpAREP catalyses REP cleavage and joining potentially important in REP proliferation. Read on

Utp23p is required for dissociation of snR30 small nucleolar RNP from pre-ribosomal particles
Coralie Hoareau-Aveilla, Eléonore Fayet-Lebaron, Beáta E. Jády, Anthony K. Henras, and Tamás Kiss

The snR30 H/ACA snoRNA is required for pre-rRNA processing and 18S production. Contrary to previous efforts made by several laboratories, apart from the four H/ACA core proteins, no specific protein partners have been identified for snR30. By using a novel RNA-based tandem affinity selection approach, we demonstrated that a fraction of yeast snR30 specifically interacts with the Utp23p and Kri1p pre-rRNA processing factors. For the first time, we identified direct functional interactions between snR30 and Utp23p and Kri1p. We demonstrated that Utp23p is required for the release of snR30 from pre-ribosomes, while incorporation of Kri1p and Utp23p into functionally active small subunit processome necessitates the snR30 snoRNP. Read on

Configuring robust DNA strand displacement reactions for in situ molecular analyses
Dzifa Y. Duose, Ryan M. Schweller, Jan Zimak, Arthur R. Rogers, Walter N. Hittelman, and Michael R. Diehl

The ability to control strand displacement reactions between dynamic oligonucleotide complexes has opened opportunities to create new classes of programmable molecular-cell detection technologies and imaging probes. Yet, even though several functional probes have been developed, the chemical properties of most dynamic oligonucleotide constructs have not been characterized extensively within cellular environments. By analyzing the efficiencies and failure modes of strand displacement reactions within fixed cell samples, this work uncovers key constraints that must be addressed to create reactive DNA systems for in situ molecular-cell analyses. Read on

Gli2 and MEF2C activate each other’s expression and function synergistically during cardiomyogenesis in vitro
Anastassia Voronova, Ashraf Al Madhoun, Anna Fischer, Michael Shelton, Christina Karamboulas, and Ilona Sylvia Skerjanc

Our findings demonstrate that Gli2, (glioma associated factor 2), a transactivator of Sonic Hedgehog (Shh) signaling, and MEF2C (myocyte enhancer factor 2C), associate with each other's gene elements and regulate each other's expression during heart muscle cell differentiation in stem cells. Furthermore, Gli2 and MEF2C were found to form a protein complex capable of synergistically activating gene promoters that participate in cardiomyogenesis. We thus propose a model whereby Gli2 and MEF2C directly activate each other’s expression and form a protein complex, which synergistically activates transcription, enhancing cardiac muscle development. This model links Shh signaling to MEF2C function during cardiomyogenesis. Read on

Genome-wide occupancy links Hoxa2 to Wnt-beta-catenin signaling in mouse embryonic development
Ian J. Donaldson, Shilu Amin, James J. Hensman, Eva Kutejova, Magnus Rattray, Neil Lawrence, Andrew Hayes, Christopher M. Ward, and Nicoletta Bobola

In this article, the authors provide an example of how transcription factors’ genome occupancy reflects biological functions. Hox transcription factors establish the body plan in the entire animal kingdom, but where in the genome Hox localize while instructing vertebrate embryonic development is unknown. By examining Hoxa2 genomic binding sites in the mouse embryo, the authors capture the developmental processes controlled by Hoxa2 and discover an unknown link between Hoxa2 and the Wnt pathway. Crucially, in vivo examination of Wnt-beta-catenin activity confirms that Wnt-beta-catenin signaling is downstream of Hoxa2. Read on

Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity
Johannes M. Freudenberg, Swati Ghosh, Brad L. Lackford, Sailu Yellaboina, Xiaofeng Zheng, Ruifang Li, Suresh Cuddapah, Paul A. Wade, Guang Hu, and Raja Jothi

TET family of enzymes (Tet1/2/3) promote DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Tet1, robustly expressed in mouse embryonic stem cells (mESCs), has been implicated in mESC maintenance. Here teh authors demonstrate that, unlike genetic deletion, RNAi-mediated depletion of Tet1 in mESCs led to a significant reduction in 5hmC and loss of mESC identity. Meta-analyses suggested interaction between Tet1 and LIF signaling. LIF is known to promote self-renewal and pluripotency in mESCs. The authors find that Tet1 depletion impaired LIF-dependent Stat3-mediated gene activation by affecting Stat3's ability to bind to its target sites. These data reveals Tet1’s normal physiological role in maintaining the pluripotent state that may be subject to homeostatic compensation in genetic models. Read on

Yin Yang 1 extends the Myc-related Transcription Factors Network in Embryonic Stem Cells
Pietro Vella, Iros Barozzi, Alessandro Cuomo, Tiziana Bonaldi, and Diego Pasini

In this article, the authors present a detailed genome-wide characterization in embryonic stem cells (ESC) of the transcriptional proprieties of Yy1. They show that Yy1 broad Polycomb-independent functions in regulating gene expression and small RNAs biogenesis by cooperating with the Myc related network of transcription factors. Such findings identify a novel player of an important network of transcription factors that is not only responsible for ESC self-renewal and differentiation but also for the ESC-like transcription signature found in malignant cancer cells. Read on

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