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      Alternative splicing and co-option of transposable elements: the case of TMPO/LAP2α and ZNF451 in mammals

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      Bioinformatics
      Oxford University Press

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          Abstract

          Summary: Transposable elements constitute a large fraction of vertebrate genomes and, during evolution, may be co-opted for new functions. Exonization of transposable elements inserted within or close to host genes is one possible way to generate new genes, and alternative splicing of the new exons may represent an intermediate step in this process. The genes TMPO and ZNF451 are present in all vertebrate lineages. Although they are not evolutionarily related, mammalian TMPO and ZNF451 do have something in common—they both code for splice isoforms that contain LAP2alpha domains. We found that these LAP2alpha domains have sequence similarity to repetitive sequences in non-mammalian genomes, which are in turn related to the first ORF from a DIRS1-like retrotransposon. This retrotransposon domestication happened separately and resulted in proteins that combine retrotransposon and host protein domains. The alternative splicing of the retrotransposed sequence allowed the production of both the new and the untouched original isoforms, which may have contributed to the success of the colonization process. The LAP2alpha-specific isoform of TMPO (LAP2α) has been co-opted for important roles in the cell, whereas the ZNF451 LAP2alpha isoform is evolving under strong purifying selection but remains uncharacterized.

          Contact: mtress@ 123456cnio.es or valencia@ 123456cnio.es

          Supplementary information: Supplementary data are available at Bioinformatics online.

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          Most cited references28

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            Datamonkey is a popular web-based suite of phylogenetic analysis tools for use in evolutionary biology. Since the original release in 2005, we have expanded the analysis options to include recently developed algorithmic methods for recombination detection, evolutionary fingerprinting of genes, codon model selection, co-evolution between sites, identification of sites, which rapidly escape host-immune pressure and HIV-1 subtype assignment. The traditional selection tools have also been augmented to include recent developments in the field. Here, we summarize the analyses options currently available on Datamonkey, and provide guidelines for their use in evolutionary biology. Availability and documentation: http://www.datamonkey.org.
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              The Rb protein is a tumor suppressor, which plays a pivotal role in the negative control of the cell cycle and in tumor progression. It has been shown that Rb protein (pRb) is responsible for a major G1 checkpoint, blocking S-phase entry and cell growth. The retinoblastoma family includes three members, Rb/p105, p107 and Rb2/p130, collectively referred to as 'pocket proteins'. The pRb protein represses gene transcription, required for transition from G1 to S phase, by directly binding to the transactivation domain of E2F and by binding to the promoter of these genes as a complex with E2F. pRb represses transcription also by remodeling chromatin structure through interaction with proteins such as hBRM, BRG1, HDAC1 and SUV39H1, which are involved in nucleosome remodeling, histone acetylation/deacetylation and methylation, respectively. Loss of pRb functions may induce cell cycle deregulation and so lead to a malignant phenotype. Gene inactivation of pRB through chromosomal mutations is one of the principal reasons for retinoblastoma tumor development. Functional inactivation of pRb by viral oncoprotein binding is also shown in many neoplasias such as cervical cancer, mesothelioma and AIDS-related Burkitt's lymphoma.
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                Author and article information

                Journal
                Bioinformatics
                Bioinformatics
                bioinformatics
                bioinfo
                Bioinformatics
                Oxford University Press
                1367-4803
                1367-4811
                15 July 2015
                02 March 2015
                02 March 2015
                : 31
                : 14
                : 2257-2261
                Affiliations
                Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre, Madrid 28029, Spain
                Author notes
                *To whom correspondence should be addressed.

                Associate Editor: Janet Kelso

                Article
                btv132
                10.1093/bioinformatics/btv132
                4495291
                25735770
                67851be5-19a7-49fb-86a4-a1c4c4c31164
                © The Author 2015. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 December 2014
                : 29 January 2015
                : 25 February 2015
                Page count
                Pages: 5
                Categories
                Discovery Notes
                Sequence Analysis

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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