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  • 1
    Online Resource
    Online Resource
    Cold Spring Harbor Laboratory ; 2000
    In:  RNA Vol. 6, No. 3 ( 2000-3), p. 325-338
    In: RNA, Cold Spring Harbor Laboratory, Vol. 6, No. 3 ( 2000-3), p. 325-338
    Type of Medium: Online Resource
    ISSN: 1355-8382
    Language: Unknown
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2000
    detail.hit.zdb_id: 1475737-0
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Cold Spring Harbor Laboratory ; 2001
    In:  RNA Vol. 7, No. 2 ( 2001-2), p. 254-265
    In: RNA, Cold Spring Harbor Laboratory, Vol. 7, No. 2 ( 2001-2), p. 254-265
    Type of Medium: Online Resource
    ISSN: 1355-8382
    Language: Unknown
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2001
    detail.hit.zdb_id: 1475737-0
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Cold Spring Harbor Laboratory ; 2015
    In:  RNA Vol. 21, No. 6 ( 2015-06), p. 1110-1121
    In: RNA, Cold Spring Harbor Laboratory, Vol. 21, No. 6 ( 2015-06), p. 1110-1121
    Abstract: A 3D model of RNA structure can provide information about its function and regulation that is not possible with just the sequence or secondary structure. Current models suffer from low accuracy and long running times and either neglect or presume knowledge of the long-range interactions which stabilize the tertiary structure. Our coarse-grained, helix-based, tertiary structure model operates with only a few degrees of freedom compared with all-atom models while preserving the ability to sample tertiary structures given a secondary structure. It strikes a balance between the precision of an all-atom tertiary structure model and the simplicity and effectiveness of a secondary structure representation. It provides a simplified tool for exploring global arrangements of helices and loops within RNA structures. We provide an example of a novel energy function relying only on the positions of stems and loops. We show that coupling our model to this energy function produces predictions as good as or better than the current state of the art tools. We propose that given the wide range of conformational space that needs to be explored, a coarse-grain approach can explore more conformations in less iterations than an all-atom model coupled to a fine-grain energy function. Finally, we emphasize the overarching theme of providing an ensemble of predicted structures, something which our tool excels at, rather than providing a handful of the lowest energy structures.
    Type of Medium: Online Resource
    ISSN: 1355-8382 , 1469-9001
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2015
    detail.hit.zdb_id: 1475737-0
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Cold Spring Harbor Laboratory ; 2010
    In:  RNA Vol. 16, No. 7 ( 2010-07), p. 1308-1316
    In: RNA, Cold Spring Harbor Laboratory, Vol. 16, No. 7 ( 2010-07), p. 1308-1316
    Abstract: Dynamical changes of RNA secondary structures play an important role in the function of many regulatory RNAs. Such kinetic effects, especially in time-variable and externally triggered systems, are usually investigated by means of extensive and expensive simulations of large sets of individual folding trajectories. Here we describe the theoretical foundations of a generic approach that not only allows the direct computation of approximate population densities but also reduces the efforts required to analyze the folding energy landscapes to a one-time preprocessing step. The basic idea is to consider the kinetics on individual landscapes and to model external triggers and environmental changes as small but discrete changes in the landscapes. A “barmap” links macrostates of temporally adjacent landscapes and defines the transfer of population densities from one “snapshot” to the next. Implemented in the BarMap software, this approach makes it feasible to study folding processes at the level of basins, saddle points, and barriers for many nonstationary scenarios, including temperature changes, cotranscriptional folding, refolding in consequence to degradation, and mechanically constrained kinetics, as in the case of the translocation of a polymer through a pore.
    Type of Medium: Online Resource
    ISSN: 1355-8382 , 1469-9001
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2010
    detail.hit.zdb_id: 1475737-0
    SSG: 12
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  • 5
    In: RNA, Cold Spring Harbor Laboratory, Vol. 11, No. 8 ( 2005-08), p. 1181-1191
    Abstract: Retroelement RNAs serve as templates for both translation and reverse transcription into extrachromosomal DNA. DNA copies may be inserted into the host genome to multiply element sequences. This transpositional activity of retroelements is usually restricted to specific conditions, particularly to conditions that impose stress on the host organism. In this work, we examined how the mRNA initiation point, and features of primary and secondary structure, of tobacco retrotransposon Tto1 RNA influence its transpositional activity. We found that the most abundant Tto1 RNA is not a substrate for reverse transcription. It is poorly translated, and its 5′-end does not contain a region of redundancy with the most prominent 3′-end. In contrast, expression of an mRNA with the 5′-end extended by 28 nucleotides allows translation and gives rise to transposition events in the heterologous host, Arabidopsis thaliana . In addition, the presence of extended hairpins and of two short open reading frames in the 5′-leader sequence of Tto1 mRNA suggests that translation does not involve ribosome scanning from the mRNA 5′-end to the translation initiation site.
    Type of Medium: Online Resource
    ISSN: 1355-8382 , 1469-9001
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2005
    detail.hit.zdb_id: 1475737-0
    SSG: 12
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  • 6
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 17, No. 6 ( 2007-06), p. 852-864
    Abstract: Functional RNA structures play an important role both in the context of noncoding RNA transcripts as well as regulatory elements in mRNAs. Here we present a computational study to detect functional RNA structures within the ENCODE regions of the human genome. Since structural RNAs in general lack characteristic signals in primary sequence, comparative approaches evaluating evolutionary conservation of structures are most promising. We have used three recently introduced programs based on either phylogenetic–stochastic context-free grammar (EvoFold) or energy directed folding (RNAz and AlifoldZ), yielding several thousand candidate structures (corresponding to ∼2.7% of the ENCODE regions). EvoFold has its highest sensitivity in highly conserved and relatively AU-rich regions, while RNAz favors slightly GC-rich regions, resulting in a relatively small overlap between methods. Comparison with the GENCODE annotation points to functional RNAs in all genomic contexts, with a slightly increased density in 3′-UTRs. While we estimate a significant false discovery rate of ∼50%–70% many of the predictions can be further substantiated by additional criteria: 248 loci are predicted by both RNAz and EvoFold, and an additional 239 RNAz or EvoFold predictions are supported by the (more stringent) AlifoldZ algorithm. Five hundred seventy RNAz structure predictions fall into regions that show signs of selection pressure also on the sequence level (i.e., conserved elements). More than 700 predictions overlap with noncoding transcripts detected by oligonucleotide tiling arrays. One hundred seventy-five selected candidates were tested by RT-PCR in six tissues, and expression could be verified in 43 cases (24.6%).
    Type of Medium: Online Resource
    ISSN: 1088-9051
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2007
    detail.hit.zdb_id: 1483456-X
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Cold Spring Harbor Laboratory ; 2012
    In:  RNA Vol. 18, No. 5 ( 2012-05), p. 900-914
    In: RNA, Cold Spring Harbor Laboratory, Vol. 18, No. 5 ( 2012-05), p. 900-914
    Abstract: Current genomic screens for noncoding RNAs (ncRNAs) predict a large number of genomic regions containing potential structural ncRNAs. The analysis of these data requires highly accurate prediction of ncRNA boundaries and discrimination of promising candidate ncRNAs from weak predictions. Existing methods struggle with these goals because they rely on sequence-based multiple sequence alignments, which regularly misalign RNA structure and therefore do not support identification of structural similarities. To overcome this limitation, we compute columnwise and global reliabilities of alignments based on sequence and structure similarity; we refer to these st ructure-based a lignment r eliabilities as STARs. The columnwise STARs of alignments, or STAR profiles, provide a versatile tool for the manual and automatic analysis of ncRNAs. In particular, we improve the boundary prediction of the widely used ncRNA gene finder RNAz by a factor of 3 from a median deviation of 47 to 13 nt. Post-processing RNAz predictions, LocARNA-P's STAR score allows much stronger discrimination between true- and false-positive predictions than RNAz's own evaluation. The improved accuracy, in this scenario increased from AUC 0.71 to AUC 0.87, significantly reduces the cost of successive analysis steps. The ready-to-use software tool LocARNA-P produces structure-based multiple RNA alignments with associated columnwise STARs and predicts ncRNA boundaries. We provide additional results, a web server for LocARNA/LocARNA-P, and the software package, including documentation and a pipeline for refining screens for structural ncRNA, at http://www.bioinf.uni-freiburg.de/Supplements/LocARNA-P/ .
    Type of Medium: Online Resource
    ISSN: 1355-8382 , 1469-9001
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2012
    detail.hit.zdb_id: 1475737-0
    SSG: 12
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  • 8
    In: RNA, Cold Spring Harbor Laboratory, Vol. 17, No. 4 ( 2011-04), p. 578-594
    Abstract: With the availability of genome-wide transcription data and massive comparative sequencing, the discrimination of coding from noncoding RNAs and the assessment of coding potential in evolutionarily conserved regions arose as a core analysis task. Here we present RNAcode, a program to detect coding regions in multiple sequence alignments that is optimized for emerging applications not covered by current protein gene-finding software. Our algorithm combines information from nucleotide substitution and gap patterns in a unified framework and also deals with real-life issues such as alignment and sequencing errors. It uses an explicit statistical model with no machine learning component and can therefore be applied “out of the box,” without any training, to data from all domains of life. We describe the RNAcode method and apply it in combination with mass spectrometry experiments to predict and confirm seven novel short peptides in Escherichia coli and to analyze the coding potential of RNAs previously annotated as “noncoding.” RNAcode is open source software and available for all major platforms at http://wash.github.com/rnacode .
    Type of Medium: Online Resource
    ISSN: 1355-8382 , 1469-9001
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2011
    detail.hit.zdb_id: 1475737-0
    SSG: 12
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