Biomedical subjects

Anke Busch

Publications and source records attributed to Anke Busch.

5 recordsLinked to original sources

PubMed2025

DNA methylation at retrotransposons protects the germline by preventing NRF1-mediated activation.

Silencing evolutionary young retrotransposons by cytosine DNA methylation is essential for spermatogenesis, as failure to methylate their promoters leads to reactivation, meiotic failure, and infertility. How retrotransposons reactivate in the absence of DNA methylation is poorly understood. We show that upon defective DNA methylation, distinct retrotransposon families display unique expression patterns and chromatin landscapes during mouse spermatogenesis. We find that their reactivation in meiotic spermatocytes correlates with the loss of bivalent H3K4me3-H3K27me3 chromatin marks. Through proteomics and chromatin profiling, we identify NRF1 as a DNA methylation-sensitive transcription factor that transactivates unmethylated retrotransposons. Conditional germline knockout of Nrf1 in the absence of DNA methylation rescues the silencing of the most mutagenic retrotransposon in mice, namely Intracisternal A-particle or IAP. Our findings reveal that chromatin modifications together with a DNA methylation-sensitive transcription factor regulate retrotransposon expression in the absence of DNA methylation in spermatogenesis, revealing a mechanism by which retrotransposons proliferate in the germline after evading DNA methylation-based silencing.

Animals↗

PubMed2006

Using RNA secondary structures to guide sequence motif finding towards single-stranded regions.

RNA binding proteins recognize RNA targets in a sequence specific manner. Apart from the sequence, the secondary structure context of the binding site also affects the binding affinity. Binding sites are often located in single-stranded RNA regions and it was shown that the sequestration of a binding motif in a double-strand abolishes protein binding. Thus, it is desirable to include knowledge about RNA secondary structures when searching for the binding motif of a protein. We present the approach MEMERIS for searching sequence motifs in a set of RNA sequences and simultaneously integrating information about secondary structures. To abstract from specific structural elements, we precompute position-specific values measuring the single-strandedness of all substrings of an RNA sequence. These values are used as prior knowledge about the motif starts to guide the motif search. Extensive tests with artificial and biological data demonstrate that MEMERIS is able to identify motifs in single-stranded regions even if a stronger motif located in double-strand parts exists. The discovered motif occurrences in biological datasets mostly coincide with known protein-binding sites. This algorithm can be used for finding the binding motif of single-stranded RNA-binding proteins in SELEX or other biological sequence data.

Algorithms↗

PubMed2006

INFO-RNA--a fast approach to inverse RNA folding.

MOTIVATION: The structure of RNA molecules is often crucial for their function. Therefore, secondary structure prediction has gained much interest. Here, we consider the inverse RNA folding problem, which means designing RNA sequences that fold into a given structure. RESULTS: We introduce 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. For the selection of neighbors during the search, we use a kind of look-ahead of one selection step applying an additional energy-based criterion. Afterwards, the pre-ordered neighbors are tested using the actual optimization criterion of minimizing the structure distance between the target structure and the mfe structure of the considered neighbor. We compared our algorithm to RNAinverse and RNA-SSD for artificial and biological test sets. Using INFO-RNA, we performed better than RNAinverse and in most cases, we gained better results than RNA-SSD, the probably best inverse RNA folding tool on the market. AVAILABILITY: www.bioinf.uni-freiburg.de?Subpages/software.html.

Algorithms↗

PubMed2005

SECISDesign: a server to design SECIS-elements within the coding sequence.

SUMMARY: SECISDesign is 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. AVAILABILITY: The server is available at http://www.bio.inf.uni-jena.de/Software/SECISDesign/index.html.

Computer-Aided Design↗

PubMed2004

Efficient prediction of alternative splice forms using protein domain homology.

Alternative splicing can yield manifold different mature mRNAs from one precursor. New findings indicate that alternative splicing occurs much more often than previously assumed. A major goal of functional genomics lies in elucidating and characterizing the entire spectrum of alternative splice forms. Existing approaches such as EST-alignments focus only on the mRNA sequence to detect alternative splice forms. They do not consider function and characteristics of the resulting proteins. One important example of such functional characterization is homology to a known protein domain family. A powerful description of protein domains are profile Hidden Markov models (HMM) as stored in the Pfam database. In this paper we address the problem of identifying the splice form with the highest similarity to a protein domain family. Therefore, we take into consideration all possible splice forms. As demonstrated here for a number of genes, this homology based approach can be used successfully for predicting partial gene structures. Furthermore, we present some novel splice form predictions with high-scoring protein domain homology and point out that the detection of splice form specific protein domains helps to answer questions concerning hereditary diseases. Simple approaches based on a BLASTP search cannot be applied here, since the number of possible splice forms increases exponentially with the number of exons. To this end, we have developed an efficient polynomial-time algorithm, called ASFPred (Alternative Splice Form Prediction). This algorithm needs only a set of exons as input.

Algorithms↗