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Structural analysis of aligned RNAs.

Voss B - Nucleic Acids Res. (2006)

Bottom Line: For correct characterization of such classes it is therefore of great importance to analyse the structural features in great detail.RNAlishapes makes use of an extended thermodynamic model and covariance scoring, which allows to reward covariation of paired bases.Applying the algorithm to a set of bacterial trp-operon leaders using shape abstraction it was able to identify the two alternating conformations of this attenuator.

View Article: PubMed Central - PubMed

Affiliation: Experimental Bioinformatics, Institute of Biology II, Freiburg University, Schänzlestrasse 1, 79104 Freiburg, Germany. bjoern.voss@biologie.uni-freiburg.de

ABSTRACT
The knowledge about classes of non-coding RNAs (ncRNAs) is growing very fast and it is mainly the structure which is the common characteristic property shared by members of the same class. For correct characterization of such classes it is therefore of great importance to analyse the structural features in great detail. In this manuscript I present RNAlishapes which combines various secondary structure analysis methods, such as suboptimal folding and shape abstraction, with a comparative approach known as RNA alignment folding. RNAlishapes makes use of an extended thermodynamic model and covariance scoring, which allows to reward covariation of paired bases. Applying the algorithm to a set of bacterial trp-operon leaders using shape abstraction it was able to identify the two alternating conformations of this attenuator. Besides providing in-depth analysis methods for aligned RNAs, the tool also shows a fairly well prediction accuracy. Therefore, RNAlishapes provides the community with a powerful tool for structural analysis of classes of RNAs and is also a reasonable method for consensus structure prediction based on sequence alignments. RNAlishapes is available for online use and download at http://rna.cyanolab.de.

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Related in: MedlinePlus

Alternate consensus structures for trp-Attenuators. Analysis of trp-operon leaders from different Corynebacterium spp. and Streptomyces spp. (A) MmFE structure for the alignment shown in (C). The blue hairpin corresponds to the terminator hairpin. (B) Shrep of the second best shape. The consensus structure comprises the same sequence regions as the structure in (A), making these two structures mutually exclusive. (C) Alignment of eight trp-operon leaders from different Corynebacterium spp. and Streptomyces spp. Colours indicate the different stems. Bases paired in both alternative structures are coded by the mixed colour.
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fig2: Alternate consensus structures for trp-Attenuators. Analysis of trp-operon leaders from different Corynebacterium spp. and Streptomyces spp. (A) MmFE structure for the alignment shown in (C). The blue hairpin corresponds to the terminator hairpin. (B) Shrep of the second best shape. The consensus structure comprises the same sequence regions as the structure in (A), making these two structures mutually exclusive. (C) Alignment of eight trp-operon leaders from different Corynebacterium spp. and Streptomyces spp. Colours indicate the different stems. Bases paired in both alternative structures are coded by the mixed colour.

Mentions: Formation of alternating structures in mRNA leader regions is an important mechanism of gene regulation. Several variants exist, which all share the common feature of two competing structures, one of which either inhibits translation initiation or leads to premature termination of transcription. The transition between the two structures is triggered by an external effector, e.g. protein, tRNA, or is formed co-transcriptional, as in classical attenuators. One such classical attenuator is found in front of the trp-operon of several Corynebacterium spp. and Streptomyces spp., which have recently been studied in detail in (53). I extracted the sequences of the leader regions and performed a multiple sequence alignment using ClustalW with DNA parameters. Subsequently, RNAlishapes was used to predict energetically favourable consensus structures. The results are summarized in Figure 2 and show two conformations which are mutually exclusive, similar in score and also explain the attenuation mechanism. The stem-loop at the 3′ end of structure A is a terminator hairpin, leading to premature termination of transcription. It achieves a better score as structure B, resembling the fact that structure A corresponds to the native state of this conformational switch.


Structural analysis of aligned RNAs.

Voss B - Nucleic Acids Res. (2006)

Alternate consensus structures for trp-Attenuators. Analysis of trp-operon leaders from different Corynebacterium spp. and Streptomyces spp. (A) MmFE structure for the alignment shown in (C). The blue hairpin corresponds to the terminator hairpin. (B) Shrep of the second best shape. The consensus structure comprises the same sequence regions as the structure in (A), making these two structures mutually exclusive. (C) Alignment of eight trp-operon leaders from different Corynebacterium spp. and Streptomyces spp. Colours indicate the different stems. Bases paired in both alternative structures are coded by the mixed colour.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1636479&req=5

fig2: Alternate consensus structures for trp-Attenuators. Analysis of trp-operon leaders from different Corynebacterium spp. and Streptomyces spp. (A) MmFE structure for the alignment shown in (C). The blue hairpin corresponds to the terminator hairpin. (B) Shrep of the second best shape. The consensus structure comprises the same sequence regions as the structure in (A), making these two structures mutually exclusive. (C) Alignment of eight trp-operon leaders from different Corynebacterium spp. and Streptomyces spp. Colours indicate the different stems. Bases paired in both alternative structures are coded by the mixed colour.
Mentions: Formation of alternating structures in mRNA leader regions is an important mechanism of gene regulation. Several variants exist, which all share the common feature of two competing structures, one of which either inhibits translation initiation or leads to premature termination of transcription. The transition between the two structures is triggered by an external effector, e.g. protein, tRNA, or is formed co-transcriptional, as in classical attenuators. One such classical attenuator is found in front of the trp-operon of several Corynebacterium spp. and Streptomyces spp., which have recently been studied in detail in (53). I extracted the sequences of the leader regions and performed a multiple sequence alignment using ClustalW with DNA parameters. Subsequently, RNAlishapes was used to predict energetically favourable consensus structures. The results are summarized in Figure 2 and show two conformations which are mutually exclusive, similar in score and also explain the attenuation mechanism. The stem-loop at the 3′ end of structure A is a terminator hairpin, leading to premature termination of transcription. It achieves a better score as structure B, resembling the fact that structure A corresponds to the native state of this conformational switch.

Bottom Line: For correct characterization of such classes it is therefore of great importance to analyse the structural features in great detail.RNAlishapes makes use of an extended thermodynamic model and covariance scoring, which allows to reward covariation of paired bases.Applying the algorithm to a set of bacterial trp-operon leaders using shape abstraction it was able to identify the two alternating conformations of this attenuator.

View Article: PubMed Central - PubMed

Affiliation: Experimental Bioinformatics, Institute of Biology II, Freiburg University, Schänzlestrasse 1, 79104 Freiburg, Germany. bjoern.voss@biologie.uni-freiburg.de

ABSTRACT
The knowledge about classes of non-coding RNAs (ncRNAs) is growing very fast and it is mainly the structure which is the common characteristic property shared by members of the same class. For correct characterization of such classes it is therefore of great importance to analyse the structural features in great detail. In this manuscript I present RNAlishapes which combines various secondary structure analysis methods, such as suboptimal folding and shape abstraction, with a comparative approach known as RNA alignment folding. RNAlishapes makes use of an extended thermodynamic model and covariance scoring, which allows to reward covariation of paired bases. Applying the algorithm to a set of bacterial trp-operon leaders using shape abstraction it was able to identify the two alternating conformations of this attenuator. Besides providing in-depth analysis methods for aligned RNAs, the tool also shows a fairly well prediction accuracy. Therefore, RNAlishapes provides the community with a powerful tool for structural analysis of classes of RNAs and is also a reasonable method for consensus structure prediction based on sequence alignments. RNAlishapes is available for online use and download at http://rna.cyanolab.de.

Show MeSH
Related in: MedlinePlus