Biomedical subjects

Andrea Tanzer

Publications and source records attributed to Andrea Tanzer.

6 recordsLinked to original sources

PubMed2007

RNAs everywhere: genome-wide annotation of structured RNAs.

Starting with the discovery of microRNAs and the advent of genome-wide transcriptomics, non-protein-coding transcripts have moved from a fringe topic to a central field research in molecular biology. In this contribution we review the state of the art of "computational RNomics", i.e., the bioinformatics approaches to genome-wide RNA annotation. Instead of rehashing results from recently published surveys in detail, we focus here on the open problem in the field, namely (functional) annotation of the plethora of putative RNAs. A series of exploratory studies are used to provide non-trivial examples for the discussion of some of the difficulties.

Biological Evolution↗

PubMed2006

The expansion of the metazoan microRNA repertoire.

BACKGROUND: MicroRNAs have been identified as crucial regulators in both animals and plants. Here we report on a comprehensive comparative study of all known miRNA families in animals. We expand the MicroRNA Registry 6.0 by more than 1000 new homologs of miRNA precursors whose expression has been verified in at least one species. Using this uniform data basis we analyze their evolutionary history in terms of individual gene phylogenies and in terms of preservation of genomic nearness across species. This allows us to reliably identify microRNA clusters that are derived from a common transcript. RESULTS: We identify three episodes of microRNA innovation that correspond to major developmental innovations: A class of about 20 miRNAs is common to protostomes and deuterostomes and might be related to the advent of bilaterians. A second large wave of innovations maps to the branch leading to the vertebrates. The third significant outburst of miRNA innovation coincides with placental (eutherian) mammals. In addition, we observe the expected expansion of the microRNA inventory due to genome duplications in early vertebrates and in an ancestral teleost. The non-local duplications in the vertebrate ancestor are predated by local (tandem) duplications leading to the formation of about a dozen ancient microRNA clusters. CONCLUSION: Our results suggest that microRNA innovation is an ongoing process. Major expansions of the metazoan miRNA repertoire coincide with the advent of bilaterians, vertebrates, and (placental) mammals.

Animals↗

PubMed2006

Evolution of microRNAs.

MicroRNAs (miRNAs) form a large class of small regulatory RNAs in eukaryotes. Although they share a common processing pathway and certain structural features, in general, there is no detectable sequence similarity among miRNAs from a given organism. On the other hand, many miRNAs are members of a family of a few, often very similar, paralogs. It is, thus, of interest to trace the evolutionary history of individual miRNAs, to identify the timing of gene duplications, and to study relationships between the histories of different miRNA families. Some miRNAs are transcribed from polycistronic primary transcripts. In these cases, we will study the evolution of entire clusters.

Base Pairing↗

PubMed2005

Comparative promoter region analysis powered by CORG.

BACKGROUND: Promoters are key players in gene regulation. They receive signals from various sources (e.g. cell surface receptors) and control the level of transcription initiation, which largely determines gene expression. In vertebrates, transcription start sites and surrounding regulatory elements are often poorly defined. To support promoter analysis, we present CORG http://corg.molgen.mpg.de, a framework for studying upstream regions including untranslated exons (5' UTR). DESCRIPTION: The automated annotation of promoter regions integrates information of two kinds. First, statistically significant cross-species conservation within upstream regions of orthologous genes is detected. Pairwise as well as multiple sequence comparisons are computed. Second, binding site descriptions (position-weight matrices) are employed to predict conserved regulatory elements with a novel approach. Assembled EST sequences and verified transcription start sites are incorporated to distinguish exonic from other sequences. As of now, we have included 5 species in our analysis pipeline (man, mouse, rat, fugu and zebrafish). We characterized promoter regions of 16,127 groups of orthologous genes. All data are presented in an intuitive way via our web site. Users are free to export data for single genes or access larger data sets via our DAS server http://tomcat.molgen.mpg.de:8080/das. The benefits of our framework are exemplarily shown in the context of phylogenetic profiling of transcription factor binding sites and detection of microRNAs close to transcription start sites of our gene set. CONCLUSION: The CORG platform is a versatile tool to support analyses of gene regulation in vertebrate promoter regions. Applications for CORG cover a broad range from studying evolution of DNA binding sites and promoter constitution to the discovery of new regulatory sequence elements (e.g. microRNAs and binding sites).

5' Untranslated Regions↗

PubMed2005

Evolution of microRNAs located within Hox gene clusters.

MicroRNAs (miRNAs) form an abundant class of non-coding RNA genes that have an important function in post-transcriptional gene regulation and in particular modulate the expression of developmentally important transcription factors including Hox genes. Two families of microRNAs are genomically located in intergenic regions in the Hox clusters of vertebrates. Here we describe their evolution in detail. We show that the micro RNAs closely follow the patterns of protein evolution in the Hox clusters, which is characterized by cluster duplications followed by differential gene loss.

Animals↗

PubMed2004

Molecular evolution of a microRNA cluster.

Many of the known microRNAs are encoded in polycistronic transcripts. Here, we reconstruct the evolutionary history of the mir17 microRNA clusters which consist of miR-17, miR-18, miR-19a, miR-19b, miR-20, miR-25, miR-92, miR-93, miR-106a, and miR-106b. The history of this cluster is governed by an initial phase of local (tandem) duplications, a series of duplications of entire clusters and subsequent loss of individual microRNAs from the resulting paralogous clusters. The complex history of the mir17 microRNA family appears to be closely linked to the early evolution of the vertebrate lineage.

Animals↗