Bioinformatics
Institute of Computer Science
University Freiburg
de

RNA Structure

Local Sequence-Structure Alignment of RNA

In this project, we study the alignment of RNA using sequence and structure information of the molecules. A special focus of the project is on local alignment of RNAs.

The most recent outcome of the project is the tool LocARNA, which was already successfully applied for genome-wide clustering of ncRNAs. In prior work, we focussed on a specialized form of locality for RNAs, structural locality, and developed the algorithm LSSA for local sequence structure alignment.

LocARNA is a tool for producing high-quality pairwise and multiple alignment of RNA sequences. It uses a complex RNA energy model for simultaneous folding and sequence/structure alignment of the RNAs. LocARNA performs global, sequence local, or even structurally local alignment of the molecules.

The tool LocARNA and the older LSSA are available for download as source code from our Software page.

Contributing group members

Main Publications

Cooperations

Inverse RNA Folding

Here, we consider the inverse RNA folding problem, that means designing RNA sequences that fold into a given structure. We develop a new algorithm for the inverse folding problem (INFO-RNA) that consists of two parts: a dynamic programming method for good initial sequences and a following improved stochastic local search that uses an effective neighbor selection method. During the initialization, we design a sequence that among all sequences adopts the given structure with the lowest possible energy.

Software/Webserver: INFO-RNA

We present a free version of the source code of INFO-RNA 1.0 and INFO-RNA 2.0, which can be downloaded here . Furthermore, you can design your sequence online.

Contributing group members

Main Publications

Identifikation regulatorischer RNAs

Die stetig wachsende Anzahl von experimentell identifizierten regulatorischen RNAs in Bakterien macht deutlich, dass RNAs eine entscheidende Rolle bei der Regulation der Genexpression haben. Eine große Klasse dieser bakteriellen regulatorischen RNAs bindet ihre Zielgene über Basenpaarung, wodurch sich die Translationrate und/oder Stabilität der Zielgene ändert. Unsere Arbeitsgruppe beschäftigt sich mit der Entwicklung von effizienten Algorithmen zur Vorhersage von Interaktionen zwischen solchen regulatorischen RNAs und ihren Zielgenen. Die von uns entwickelten Programme werden vorrangig zur genomweiten Vorhersage von potenziellen Zielgenen in diversen Bakterienarten eingesetzt. Damit ermöglichen wir eine funktionale Charakterisierung von neu identifizierten regulatorischen RNAs in silico.

Contributing group members

Selenoproteins and Protein Design

Selenoproteins contain the 21th amino acid Selenocysteine, which is encoded by the STOP-codon UGA. For its insertion it requires a specific mRNA sequence downstream the UGA-codon that forms a hairpin-like structure (called Sec insertion sequence (SECIS)). Selenoproteins have gained much interest recently since they are very important for human health. In contrast, very little is known about selenoproteins. One reason for this is that one is not able to produce enough amount of selenoproteins by using recombinant expression in a system like E.coli. The reason is that the insertion mechanisms are different between E.coli and eukaryotes. Thus, one has to redesign the human/mammalian selenoprotein for the expression in E.coli. Here, we developed an polynomial-time algorithm for solving the computational problem involved in this design.

Webserver: SECISDesign

SECISDesign-logo Design your SECIS-element on the web.
We present a server for the design of SECIS-elements and arbitrary RNA-elements within the coding sequence of an mRNA. The element has to satisfy both structure and sequence constraints. At the same time, a certain amino acid similarity to the original protein has to be kept. The designed sequence can be used for recombinant expression of selenoproteins in Escherichia coli.

Contributing group members

Main Publications

Related Research Topics

Coarse Energy Landscape Representations for RNA Molecules

barrier tree Based on the energy landscape library, a set of tools to investigate the structure and topology of RNA energy landscapes has been implemented. These programs allow for:
Click here for further details

MARNA: Multiple Alignment of RNA

Multiple alignments of RNAs are an essential prerequisite to further analyzes such as homology modelling, motif description or illustration of conserved or variable binding sites. Beyond the comparison of RNAs on the sequence level, structural conformations determined by base-pairs have to be taken into account. Several pairwise sequence-structure alignment methods have been developed. They use extended alignment scores that evaluate secondary structure information in addition to sequence information. However, two problems for the multiple alignment step remain. First, how to combine pairwise sequence-structure alignments into a multiple alignment and second, how to generate secondary structure information for sequences whose structural information is missing. MARNA is an approach for multiple alignment of RNAs taking into considerations both the primary sequences and the secondary structures. It relies on the pairwise sequence-structure comparison strategy by generating a set of weighted alignment edges. This set is processed by a consistency-based multiple alignment method. Additionally, MARNA extracts a consensus- sequence and structure from this generated multiple alignment. MARNA can be accessed via the MARNA webpage .

Contributing group members

Main Publications