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  • 1
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder ...
    Type of Medium: Electronic Resource
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  • 2
    Publication Date: 2007-10-26
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 3
    Publication Date: 2016-08-05
    Description: MicroRNAs are small (~22 nt) noncoding RNAs that repress translation and therefore regulate the production of proteins from specific target mRNAs. microRNAs have been found to function in diverse aspects of gene regulation within animal development and many other processes. Among invertebrates, both conserved and novel, lineage specific, microRNAs have been extensively studied predominantly in holometabolous insects such as Drosophila melanogaster . However little is known about microRNA repertoires in other arthropod lineages such as the chelicerates. To understand the evolution of microRNAs in this poorly sampled subphylum, we characterized the microRNA repertoire expressed during embryogenesis of the common house spider Parasteatoda tepidariorum . We identified a total of 148 microRNAs in P. tepidariorum representing 66 families. Approximately half of these microRNA families are conserved in other metazoans, while the remainder are specific to this spider. Of the 35 conserved microRNAs families 15 had at least two copies in the P. tepidariorum genome. A BLAST-based approach revealed a similar pattern of duplication in other spiders and a scorpion, but not among other chelicerates and arthropods, with the exception of a horseshoe crab. Among the duplicated microRNAs we found examples of lineage-specific tandem duplications, and the duplication of entire microRNA clusters in three spiders, a scorpion, and in a horseshoe crab. Furthermore, we found that paralogs of many P. tepidariorum microRNA families exhibit arm switching, which suggests that duplication was often followed by sub- or neofunctionalization. Our work shows that understanding the evolution of microRNAs in the chelicerates has great potential to provide insights into the process of microRNA duplication and divergence and the evolution of animal development.
    Electronic ISSN: 1759-6653
    Topics: Biology
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  • 4
    Publication Date: 2015-05-12
    Description: Motivation: Many studies have investigated the differential expression of microRNAs (miRNAs) in disease states and between different treatments, tissues and developmental stages. Given a list of perturbed miRNAs, it is common to predict the shared pathways on which they act. The standard test for functional enrichment typically yields dozens of significantly enriched functional categories, many of which appear frequently in the analysis of apparently unrelated diseases and conditions. Results: We show that the most commonly used functional enrichment test is inappropriate for the analysis of sets of genes targeted by miRNAs. The hypergeometric distribution used by the standard method consistently results in significant P -values for functional enrichment for targets of randomly selected miRNAs, reflecting an underlying bias in the predicted gene targets of miRNAs as a whole. We developed an algorithm to measure enrichment using an empirical sampling approach, and applied this in a reanalysis of the gene ontology classes of targets of miRNA lists from 44 published studies. The vast majority of the miRNA target sets were not significantly enriched in any functional category after correction for bias. We therefore argue against continued use of the standard functional enrichment method for miRNA targets. Availability and implementation: A Python script implementing the empirical algorithm is freely available at http://sgjlab.org/empirical-go/ . Contact: sam.griffiths-jones@manchester.ac.uk or janine.lamb@manchester.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 5
    Publication Date: 2014-10-03
    Description: Introns in protein-coding genes are very rare in hemiascomycetous yeast genomes. It has been suggested that these species have experienced extensive intron loss during their evolution from the postulated intron-rich fungal ancestor. However, no intron-devoid yeast species have been identified and some of the introns remaining within the genomes of intron-poor species, such as Saccharomyces cerevisiae , appear to be beneficial during growth under stress conditions. In order to reveal the pattern of intron retention within intron-poor yeast species and better understand the mechanisms of intron evolution, we generated a comprehensive set of 250 orthologous introns in the 20 species that comprise the Saccharomycetaceae, by analyzing RNA deep-sequencing data and alignments of intron-containing genes. Analysis of these intron sets shows that intron loss is at least two orders of magnitude more frequent than intron gain. Fine mapping of intron positions shows that intron sliding is rare, and that introns are almost always removed without changing the primary sequence of the encoded protein. The latter finding is consistent with the prevailing view that homologous recombination between reverse-transcribed mature mRNAs and the corresponding genomic locus is the primary mechanism of intron loss. However, we also find evidence that loss of a small number of introns is mediated by micro-homology, and that the number of intron losses is diminished in yeast species that have lost the microhomology end joining and nonhomologous end joining machinery.
    Electronic ISSN: 1759-6653
    Topics: Biology
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  • 6
    Publication Date: 2014-09-26
    Description: The spatiotemporal control of gene expression is crucial for the successful completion of animal development. The evolutionary constraints on development are particularly strong for the mid-embryonic stage when body segments are specified, as evidenced by a high degree of morphological and protein-coding gene conservation during this period—a phenomenon known as the developmental hourglass. The discovery of microRNA-mediated gene control revealed an entirely new layer of complexity of the molecular networks that orchestrate development. However, the constraints on microRNA developmental expression and evolution, and the implications for animal evolution are less well understood. To systematically explore the conservation of microRNAs during development, we carried out a genome-wide comparative study of microRNA expression levels throughout the ontogenesis of two divergent fruit flies, Drosophila melanogaster and D. virilis . We show that orthologous microRNAs display highly similar temporal profiles regardless of their mutation rates, suggesting that the timely expression of microRNA genes can be more constrained than their sequence. Furthermore, transitions between key developmental events in the different species are accompanied by conserved shifts in microRNA expression profiles, with the mid-embryonic period between gastrulation and segmentation characterized by the highest similarity of microRNA expression. The conservation of microRNA expression therefore displays an hourglass pattern similar to that observed for protein-coding genes.
    Electronic ISSN: 1759-6653
    Topics: Biology
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  • 7
    Publication Date: 2013-03-13
    Description: In Drosophila melanogaster , the iab-4/iab-8 locus encodes bi-directionally transcribed microRNAs that regulate the function of flanking Hox transcription factors. We show that bi-directional transcription, temporal and spatial expression patterns and Hox regulatory function of the iab-4/iab-8 locus are conserved between fly and the beetle Tribolium castaneum . Computational predictions suggest iab-4 and iab-8 microRNAs can target common sites, and cell-culture assays confirm that iab-4 and iab-8 function overlaps on Hox target sites in both fly and beetle. However, we observe key differences in the way Hox genes are targeted. For instance, abd-A transcripts are targeted only by iab-8 in Drosophila , whereas both iab-4 and iab-8 bind to Tribolium abd-A. Our evolutionary and functional characterization of a bi-directionally transcribed microRNA establishes the iab-4/iab-8 system as a model for understanding how multiple products from sense and antisense microRNAs target common sites.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 8
    Publication Date: 2013-09-06
    Description: Genetic linkage may result in the expression of multiple products from a polycistronic transcript, under the control of a single promoter. In animals, protein-coding polycistronic transcripts are rare. However, microRNAs are frequently clustered in the genomes of animals, and these clusters are often transcribed as a single unit. The evolution of microRNA clusters has been the subject of much speculation, and a selective advantage of clusters of functionally related microRNAs is often proposed. However, the origin of microRNA clusters has not been so far explored. Here, we study the evolution of microRNA clusters in Drosophila melanogaster. We observed that the majority of microRNA clusters arose by the de novo formation of new microRNA-like hairpins in existing microRNA transcripts. Some clusters also emerged by tandem duplication of a single microRNA. Comparative genomics show that these clusters are unlikely to split or undergo rearrangements. We did not find any instances of clusters appearing by rearrangement of pre-existing microRNA genes. We propose a model for microRNA cluster evolution in which selection over one of the microRNAs in the cluster interferes with the evolution of the other linked microRNAs. Our analysis suggests that the study of microRNAs and small RNAs must consider linkage associations.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 9
    Publication Date: 2013-12-29
    Description: We describe an update of the miRBase database ( http://www.mirbase.org/ ), the primary microRNA sequence repository. The latest miRBase release (v20, June 2013) contains 24 521 microRNA loci from 206 species, processed to produce 30 424 mature microRNA products. The rate of deposition of novel microRNAs and the number of researchers involved in their discovery continue to increase, driven largely by small RNA deep sequencing experiments. In the face of these increases, and a range of microRNA annotation methods and criteria, maintaining the quality of the microRNA sequence data set is a significant challenge. Here, we describe recent developments of the miRBase database to address this issue. In particular, we describe the collation and use of deep sequencing data sets to assign levels of confidence to miRBase entries. We now provide a high confidence subset of miRBase entries, based on the pattern of mapped reads. The high confidence microRNA data set is available alongside the complete microRNA collection at http://www.mirbase.org/ . We also describe embedding microRNA-specific Wikipedia pages on the miRBase website to encourage the microRNA community to contribute and share textual and functional information.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 10
    Publication Date: 2002-09-01
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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