VARNA: Interactive drawing and editing of the RNA secondary structure.

International audienceDESCRIPTION: VARNA is a tool for the automated drawing, visualization and annotation of the secondary structure of RNA, designed as a companion software for web servers and databases. FEATURES: VARNA implements four drawing algorithms, supports input/output using the classic formats dbn, ct, bpseq and RNAML and exports the drawing as five picture formats, either pixel-based (JPEG, PNG) or vector-based (SVG, EPS and XFIG). It also allows manual modification and structural annotation of the resulting drawing using either an interactive point and click approach, within a web server or through command-line arguments. AVAILABILITY: VARNA is a free software, released under the terms of the GPLv3.0 license and available at http://varna.lri.fr. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

Distribution of graph-distances in Boltzmann ensembles of RNA secondary structures

Large RNA molecules often carry multiple functional domains whose spatial arrangement is an important determinant of their function. Pre-mRNA splicing, furthermore, relies on the spatial proximity of the splice junctions that can be separated by very long introns. Similar effects appear in the processing of RNA virus genomes. Albeit a crude measure, the distribution of spatial distances in thermodynamic equilibrium therefore provides useful information on the overall shape of the molecule can provide insights into the interplay of its functional domains. Spatial distance can be approximated by the graph-distance in RNA secondary structure. We show here that the equilibrium distribution of graph-distances between arbitrary nucleotides can be computed in polynomial time by means of dynamic programming. A naive implementation would yield recursions with a very high time complexity of O(n^11). Although we were able to reduce this to O(n^6) for many practical applications a further reduction seems difficult. We conclude, therefore, that sampling approaches, which are much easier to implement, are also theoretically favorable for most real-life applications, in particular since these primarily concern long-range interactions in very large RNA molecules.Comment: Peer-reviewed and presented as part of the 13th Workshop on Algorithms in Bioinformatics (WABI2013

Steric antisense inhibition of AMPA receptor Q/R editing reveals tight coupling to intronic editing sites and splicing

Adenosine-to-Inosine (A-to-I) RNA editing is a post-transcriptional mechanism, evolved to diversify the transcriptome in metazoa. In addition to wide-spread editing in non-coding regions protein recoding by RNA editing allows for fine tuning of protein function. Functional consequences are only known for some editing sites and the combinatorial effect between multiple sites (functional epistasis) is currently unclear. Similarly, the interplay between RNA editing and splicing, which impacts on post-transcriptional gene regulation, has not been resolved. Here, we describe a versatile antisense approach, which will aid resolving these open questions. We have developed and characterized morpholino oligos targeting the most efficiently edited site--the AMPA receptor GluA2 Q/R site. We show that inhibition of editing closely correlates with intronic editing efficiency, which is linked to splicing efficiency. In addition to providing a versatile tool our data underscore the unique efficiency of a physiologically pivotal editing site

Nyanyian Syukuran Panen Dalam Ibadah Gereja Toraja Jemaat Hermon Manggasa’ Makale Tana Toraja”

ABSTRAK Penelitian ini bertujuan untuk memperoleh data yang jelas dan actual tentang : 1) Bentuk Penyajian Nyanyian Syukuran Panen Dalam Ibadah Gereja Toraja Jemaat Hermon Manggasa’. 2) Makna Nyanyian Syukuran Panen Dalam Ibadah Gereja Toraja Jemaat Hermon Manggasa’. Penelitian ini bersifat deskriptif kualitatif yang bertujuan untuk mengetahui bentuk penyajian dan makna nyanyian syukuran panen dalam ibadah Gereja Toraja Jemaat Hermon Manggasa’ Makale Tana Toraja. Teknik pengumpulan data dilakukan melalui Wawancara dan Dokumentasi. Hasil penelitian menunjukkan bahwa: 1) Bentuk penyajian Nyanyian Syukuran Panen dalam Ibadah Gereja Toraja Jemaat Hermon Manggasa’ adalah penyampaian (pa’rampoan) oleh pemimpin ibadah, dinyanyikan oleh seluruh jemaat secara unisono (satu suara) dan diiringi oleh organis. 2) Makna Nyanyian Syukuran Toraja Ibadah Gereja Toraja Jemaat Hermon Manggasa’ adalah makna semiologi yang mencakup pesan dan amanat yang terdiri atas tiga poin yaitu, Puang perangina’ mati’: doa dan pengharapan. Apamo la kipenomban: kerendahan hati, Pemala’ pa’pudiangki: ungkapan rasa syukur. Kata kunci: Nyanyian syukuran panen, Ibadah Gereja Toraja Jemaat Hermon Manggasa’

High-Performance, Radiation-Hardened Electronics for Space and Lunar Environments

The Radiation Hardened Electronics for Space Environments (RHESE) project develops advanced technologies needed for high performance electronic devices that will be capable of operating within the demanding radiation and thermal extremes of the space, lunar, and Martian environment. The technologies developed under this project enhance and enable avionics within multiple mission elements of NASA's Vision for Space Exploration. including the Constellation program's Orion Crew Exploration Vehicle. the Lunar Lander project, Lunar Outpost elements, and Extra Vehicular Activity (EVA) elements. This paper provides an overview of the RHESE project and its multiple task tasks, their technical approaches, and their targeted benefits as applied to NASA missions

Understanding the errors of SHAPE-directed RNA structure modeling

Single-nucleotide-resolution chemical mapping for structured RNA is being rapidly advanced by new chemistries, faster readouts, and coupling to computational algorithms. Recent tests have shown that selective 2'-hydroxyl acylation by primer extension (SHAPE) can give near-zero error rates (0-2%) in modeling the helices of RNA secondary structure. Here, we benchmark the method using six molecules for which crystallographic data are available: tRNA(phe) and 5S rRNA from Escherichia coli, the P4-P6 domain of the Tetrahymena group I ribozyme, and ligand-bound domains from riboswitches for adenine, cyclic di-GMP, and glycine. SHAPE-directed modeling of these highly structured RNAs gave an overall false negative rate (FNR) of 17% and a false discovery rate (FDR) of 21%, with at least one helix prediction error in five of the six cases. Extensive variations of data processing, normalization, and modeling parameters did not significantly mitigate modeling errors. Only one varation, filtering out data collected with deoxyinosine triphosphate during primer extension, gave a modest improvement (FNR = 12%, and FDR = 14%). The residual structure modeling errors are explained by the insufficient information content of these RNAs' SHAPE data, as evaluated by a nonparametric bootstrapping analysis. Beyond these benchmark cases, bootstrapping suggests a low level of confidence (<50%) in the majority of helices in a previously proposed SHAPE-directed model for the HIV-1 RNA genome. Thus, SHAPE-directed RNA modeling is not always unambiguous, and helix-by-helix confidence estimates, as described herein, may be critical for interpreting results from this powerful methodology.Comment: Biochemistry, Article ASAP (Aug. 15, 2011

Activity-regulated RNA editing in select neuronal subfields in hippocampus

RNA editing by adensosine deaminases is a widespread mechanism to alter genetic information in metazoa. In addition to modifications in non-coding regions, editing contributes to diversification of protein function, in analogy to alternative splicing. However, although splicing programs respond to external signals, facilitating fine tuning and homeostasis of cellular functions, a similar regulation has not been described for RNA editing. Here, we show that the AMPA receptor R/G editing site is dynamically regulated in the hippocampus in response to activity. These changes are bi-directional, reversible and correlate with levels of the editase Adar2. This regulation is observed in the CA1 hippocampal subfield but not in CA3 and is thus subfield/celltype-specific. Moreover, alternative splicing of the flip/flop cassette downstream of the R/G site is closely linked to the editing state, which is regulated by Ca(2+). Our data show that A-to-I RNA editing has the capacity to tune protein function in response to external stimuli