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Shmuel Pietrokovski - One of the best experts on this subject based on the ideXlab platform.

  • New types of Conserved Sequence domains in DNA-binding regions of homing endonucleases
    Trends in Biochemical Sciences, 2003
    Co-Authors: Einat Sitbon, Shmuel Pietrokovski
    Abstract:

    We have identified four new types of short Conserved Sequence domains in homing endonucleases and related proteins. These domains are modular, appearing in various combinations. One domain includes a motif known by structure as a novel Sequence-specific DNA-binding helix. Sequence similarity shows two other domains to be new types of helix-turn-helix DNA-binding domains. We term the new domains nuclease-associated modular DNA-binding domains (NUMODs).

  • searching databases of Conserved Sequence regions by aligning protein multiple alignments
    Nucleic Acids Research, 1996
    Co-Authors: Shmuel Pietrokovski
    Abstract:

    A general searching method for comparing multiple Sequence alignments was developed to detect Sequence relationships between Conserved protein regions. Multiple alignments are treated as Sequences of amino acid distributions and aligned by comparing pairs of such distributions. Four different comparison measures were tested and the Pearson correlation coefficient chosen. The method is sensitive, detecting weak Sequence relationships between protein families. Relationships are detected beyond the range of conventional Sequence database searches, illustrating the potential usefulness of the method. The previously undetected relation between flavoprotein subunits of two oxidoreductase families points to the potential active site in one of the families. The similarity between the bacterial RecA, DnaA and Rad51 protein families reveals a region in DnaA and Rad51 proteins likely to bind and unstack single-stranded DNA. Helix‐turn‐helix DNA binding domains from diverse proteins are readily detected and shown to be similar to each other. Glycosylasparaginase and gamma-glutamyltransferase enzymes are found to be similar in their proteolytic cleavage sites. The method has been fully implemented on the World Wide Web at URL: http://blocks.fhcrc.org/blocks-bin/LAMA_search

  • Conserved Sequence features of inteins protein introns and their use in identifying new inteins and related proteins
    Protein Science, 1994
    Co-Authors: Shmuel Pietrokovski
    Abstract:

    Inteins (protein introns) are internal portions of protein Sequences that are posttranslationally excised while the flanking regions are spliced together, making an additional protein product. Inteins have been found in a number of homologous genes in yeast, mycobacteria, and extreme thermophile archaebacteria. The inteins are probably multifunctional, autocatalyzing their own splicing, and some were also shown to be DNA endonucleases. The splice junction regions and two regions similar to homing endonucleases were thought to be the only common Sequence features of inteins. This work analyzed all published intein Sequences with recently developed methods for detecting weak, Conserved Sequence features. The methods complemented each other in the identification and assessment of several patterns characterizing the intein Sequences. New intein Conserved features are discovered and the known ones are quantitatively described and localized. The general Sequence description of all the known inteins is derived from the motifs and their relative positions. The intein Sequence description is used to search the Sequence databases for intein-like proteins. A Sequence region in a mycobacterial open reading frame possessing all of the intein motifs and absent from Sequences homologous to both of its flanking Sequences is identified as an intein. A newly discovered putative intein in red algae chloroplasts is found not to contain the endonuclease motifs present in all other inteins. The yeast HO endonuclease is found to have an overall intein-like structure and a few viral polyprotein cleavage sites are found to be significantly similar to the inteins amino-end splice junction motif. The intein features described may serve for detection of intein Sequences.

Reinhard Luhrmann - One of the best experts on this subject based on the ideXlab platform.

  • snrnp sm proteins share two evolutionarily Conserved Sequence motifs which are involved in sm protein protein interactions
    The EMBO Journal, 1995
    Co-Authors: H Hermann, P Fabrizio, Veronica A Raker, K Foulaki, H Hornig, H Brahms, Reinhard Luhrmann
    Abstract:

    Abstract The spliceosomal small nuclear ribonucleoproteins (snRNPs) U1, U2, U4/U6 and U5 share eight proteins B', B, D1, D2, D3, E, F and G which form the structural core of the snRNPs. This class of common proteins plays an essential role in the biogenesis of the snRNPs. In addition, these proteins represent the major targets for the so-called anti-Sm auto-antibodies which are diagnostic for systemic lupus erythematosus (SLE). We have characterized the proteins F and G from HeLa cells by cDNA cloning, and, thus, all human Sm protein Sequences are now available for comparison. Similar to the D, B/B' and E proteins, the F and G proteins do not possess any of the known RNA binding motifs, suggesting that other types of RNA-protein interactions occur in the snRNP core. Strikingly, the eight human Sm proteins possess mutual homology in two regions, 32 and 14 amino acids long, that we term Sm motifs 1 and 2. The Sm motifs are evolutionarily highly Conserved in all of the putative homologues of the human Sm proteins identified in the data base. These results suggest that the Sm proteins may have arisen from a single common ancestor. Several hypothetical proteins, mainly of plant origin, that clearly contain the Conserved Sm motifs but exhibit only comparatively low overall homology to one of the human Sm proteins, were identified in the data base. This suggests that the Sm motifs may also be shared by non-spliceosomal proteins. Further, we provide experimental evidence that the Sm motifs are involved, at least in part, in Sm protein-protein interactions. Specifically, we show by co-immunoprecipitation analyses of in vitro translated B' and D3 that the Sm motifs are essential for complex formation between B' and D3. Our finding that the Sm proteins share Conserved Sequence motifs may help to explain the frequent occurrence in patient sera of anti-Sm antibodies that cross-react with multiple Sm proteins and may ultimately further our understanding of how the snRNPs act as auto-antigens and immunogens in SLE.

Oskar Marinbejar - One of the best experts on this subject based on the ideXlab platform.

  • the human lncrna linc pint inhibits tumor cell invasion through a highly Conserved Sequence element
    Genome Biology, 2017
    Co-Authors: Jovanna González, Dannys Martinez, Alejandro Athie, Xabier Morales, Mikel Galduroz, Ivan Raimondi, Elena Grossi, Oskar Marinbejar, Ana Rouzaut
    Abstract:

    It is now obvious that the majority of cellular transcripts do not code for proteins, and a significant subset of them are long non-coding RNAs (lncRNAs). Many lncRNAs show aberrant expression in cancer, and some of them have been linked to cell transformation. However, the underlying mechanisms remain poorly understood and it is unknown how the Sequences of lncRNA dictate their function. Here we characterize the function of the p53-regulated human lncRNA LINC-PINT in cancer. We find that LINC-PINT is downregulated in multiple types of cancer and acts as a tumor suppressor lncRNA by reducing the invasive phenotype of cancer cells. A cross-species analysis identifies a highly Conserved Sequence element in LINC-PINT that is essential for its function. This Sequence mediates a specific interaction with PRC2, necessary for the LINC-PINT-dependent repression of a pro-invasion signature of genes regulated by the transcription factor EGR1. Our findings support a Conserved functional co-dependence between LINC-PINT and PRC2 and lead us to propose a new mechanism where the lncRNA regulates the availability of free PRC2 at the proximity of co-regulated genomic loci.

H Hermann - One of the best experts on this subject based on the ideXlab platform.

  • snrnp sm proteins share two evolutionarily Conserved Sequence motifs which are involved in sm protein protein interactions
    The EMBO Journal, 1995
    Co-Authors: H Hermann, P Fabrizio, Veronica A Raker, K Foulaki, H Hornig, H Brahms, Reinhard Luhrmann
    Abstract:

    Abstract The spliceosomal small nuclear ribonucleoproteins (snRNPs) U1, U2, U4/U6 and U5 share eight proteins B', B, D1, D2, D3, E, F and G which form the structural core of the snRNPs. This class of common proteins plays an essential role in the biogenesis of the snRNPs. In addition, these proteins represent the major targets for the so-called anti-Sm auto-antibodies which are diagnostic for systemic lupus erythematosus (SLE). We have characterized the proteins F and G from HeLa cells by cDNA cloning, and, thus, all human Sm protein Sequences are now available for comparison. Similar to the D, B/B' and E proteins, the F and G proteins do not possess any of the known RNA binding motifs, suggesting that other types of RNA-protein interactions occur in the snRNP core. Strikingly, the eight human Sm proteins possess mutual homology in two regions, 32 and 14 amino acids long, that we term Sm motifs 1 and 2. The Sm motifs are evolutionarily highly Conserved in all of the putative homologues of the human Sm proteins identified in the data base. These results suggest that the Sm proteins may have arisen from a single common ancestor. Several hypothetical proteins, mainly of plant origin, that clearly contain the Conserved Sm motifs but exhibit only comparatively low overall homology to one of the human Sm proteins, were identified in the data base. This suggests that the Sm motifs may also be shared by non-spliceosomal proteins. Further, we provide experimental evidence that the Sm motifs are involved, at least in part, in Sm protein-protein interactions. Specifically, we show by co-immunoprecipitation analyses of in vitro translated B' and D3 that the Sm motifs are essential for complex formation between B' and D3. Our finding that the Sm proteins share Conserved Sequence motifs may help to explain the frequent occurrence in patient sera of anti-Sm antibodies that cross-react with multiple Sm proteins and may ultimately further our understanding of how the snRNPs act as auto-antigens and immunogens in SLE.

Graziano Pesole - One of the best experts on this subject based on the ideXlab platform.

  • Statistical assessment of discriminative features for protein-coding and non coding cross-species Conserved Sequence elements.
    BMC Bioinformatics, 2009
    Co-Authors: Teresa Maria Creanza, Flavio Mignone, David S. Horner, Annarita D'addabbo, Rosalia Maglietta, Nicola Ancona, Graziano Pesole
    Abstract:

    Background The identification of protein coding elements in sets of mammalian Conserved elements is one of the major challenges in the current molecular biology research. Many features have been proposed for automatically distinguishing coding and non coding Conserved Sequences, making so necessary a systematic statistical assessment of their differences. A comprehensive study should be composed of an association study, i.e. a comparison of the distributions of the features in the two classes, and a prediction study in which the prediction accuracies of classifiers trained on single and groups of features are analyzed, conditionally to the compared species and to the Sequence lengths.

  • Genome-wide identification of coding and non-coding Conserved Sequence tags in human and mouse genomes
    BMC Genomics, 2008
    Co-Authors: Flavio Mignone, Giorgio Grillo, Anna Anselmo, Giacinto Donvito, Giorgio Maggi, Graziano Pesole
    Abstract:

    The accurate detection of genes and the identification of functional regions is still an open issue in the annotation of genomic Sequences. This problem affects new genomes but also those of very well studied organisms such as human and mouse where, despite the great efforts, the inventory of genes and regulatory regions is far from complete. Comparative genomics is an effective approach to address this problem. Unfortunately it is limited by the computational requirements needed to perform genome-wide comparisons and by the problem of discriminating between Conserved coding and non-coding Sequences. This discrimination is often based (thus dependent) on the availability of annotated proteins. In this paper we present the results of a comprehensive comparison of human and mouse genomes performed with a new high throughput grid-based system which allows the rapid detection of Conserved Sequences and accurate assessment of their coding potential. By detecting clusters of coding Conserved Sequences the system is also suitable to accurately identify potential gene loci. Following this analysis we created a collection of human-mouse Conserved Sequence tags and carefully compared our results to reliable annotations in order to benchmark the reliability of our classifications. Strikingly we were able to detect several potential gene loci supported by EST Sequences but not corresponding to as yet annotated genes. Here we present a new system which allows comprehensive comparison of genomes to detect Conserved coding and non-coding Sequences and the identification of potential gene loci. Our system does not require the availability of any annotated Sequence thus is suitable for the analysis of new or poorly annotated genomes.

  • A high performance grid-web service framework for the identification of 'Conserved Sequence tags'
    Future Generation Computer Systems, 2007
    Co-Authors: Danilo Carrabino, Nico Sanna, Tiziana Castrignanò, Giorgio Grillo, Flavio Licciulli, Sabino Liuni, Matteo Re, Flavio Mignone, Graziano Pesole
    Abstract:

    The continuous increasing of computing power in biological research places a threshold to the single host use and suggests an approach based on distributed computing. An emerging solution is grid technology, which allows organization to make better use of existing computing resources by providing them with a single, transparent, aggregated source of computing power. Equally, bioinformatics analysis often involves many web services, allowing shared access to information and helping the biologist to design, describe, record complex experiments. A new generation of grid infrastructure, where web services are building blocks, allow managent of a web services workflow. This work shows a tool for the identification and functional annotation of 'Conserved Sequence Tags' (CSTs) through cross-species genome comparisons, deployed on a Grid System Architecture, based on Web Services concepts and technologies.

  • GenoMiner: a tool for genome-wide search of coding and non-coding Conserved Sequence tags
    Bioinformatics, 2005
    Co-Authors: Tiziana Castrignanò, Giorgio Grillo, Sabino Liuni, Flavio Mignone, Ivano Giuseppe Talamo, Graziano Pesole
    Abstract:

    Summary: GenoMiner is a software tool that searches for regions of similarity between user-submitted genome or transcript Sequences and user-specified whole genome assemblies. The program then identifies Conserved Sequence tags (CSTs) in these homologous regions and provides a prediction of their coding or non-coding nature. The analysis is carried out through three steps: (1) definition of Sequence regions homologous to the query Sequence in the selected target genomes by a fast BLAT alignment; (2) identification of CSTs by a more sensitive BLAST-like alignment between the query and the homologous regions in the target genomes and (3) assessment of the coding or non-coding nature of detected CSTs through the computation of a suitable coding potential score. GenoMiner allows the user to search the query Sequence against a number of vertebrate genome assemblies in a single run providing a user-friendly graphical output. Availability: http://www.caspur.it/GenoMiner/. GenoMiner software and documentation is available from the authors upon request. Contact: graziano.pesole@unimi.it

  • CSTminer: a web tool for the identification of coding and noncoding Conserved Sequence tags through cross-species genome comparison.
    Nucleic acids research, 2004
    Co-Authors: Tiziana Castrignanò, Giorgio Grillo, Sabino Liuni, Flavio Mignone, Alessandro Canali, Graziano Pesole
    Abstract:

    The identification and characterization of genome tracts that are highly Conserved across species during evolution may contribute significantly to the functional annotation of whole-genome Sequences. Indeed, such Sequences are likely to correspond to known or unknown coding exons or regulatory motifs. Here, we present a web server implementing a previously developed algorithm that, by comparing user-submitted genome Sequences, is able to identify statistically significant Conserved blocks and assess their coding or noncoding nature through the measure of a coding potential score. The web tool, available at http://www.caspur.it/CSTminer/, is dynamically interconnected with the Ensembl genome resources and produces a graphical output showing a map of detected Conserved Sequences and annotated gene features.