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      Conserved principles of mammalian transcriptional regulation revealed by RNA half-life

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          Abstract

          RNA levels in a cell are regulated by the relative rates of RNA synthesis and decay. We recently developed a new approach for measuring both RNA synthesis and decay in a single experimental setting by biosynthetic labeling of newly transcribed RNA. Here, we show that this provides measurements of RNA half-lives from microarray data with a so far unreached accuracy. Based on such measurements of RNA half-lives for human B-cells and mouse fibroblasts, we identified conserved regulatory principles for a large number of biological processes. We show that different regulatory patterns between functionally similar proteins are characterized by differences in the half-life of the corresponding transcripts and can be identified by measuring RNA half-life. We identify more than 100 protein families which show such differential regulatory patterns in both species. Additionally, we provide strong evidence that the activity of protein complexes consisting of subunits with overall long transcript half-lives can be regulated by transcriptional regulation of individual key subunits with short-lived transcripts. Based on this observation, we predict more than 100 key regulatory subunits for human complexes of which 28% could be confirmed in mice ( P < 10 −9). Therefore, this atlas of transcript half-lives provides new fundamental insights into many cellular processes.

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          Most cited references41

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Gene Ontology: tool for the unification of biology

            Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
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              Ensembl 2009

              The Ensembl project (http://www.ensembl.org) is a comprehensive genome information system featuring an integrated set of genome annotation, databases, and other information for chordate, selected model organism and disease vector genomes. As of release 51 (November 2008), Ensembl fully supports 45 species, and three additional species have preliminary support. New species in the past year include orangutan and six additional low coverage mammalian genomes. Major additions and improvements to Ensembl since our previous report include a major redesign of our website; generation of multiple genome alignments and ancestral sequences using the new Enredo-Pecan-Ortheus pipeline and development of our software infrastructure, particularly to support the Ensembl Genomes project (http://www.ensemblgenomes.org/).
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                September 2009
                September 2009
                26 June 2009
                26 June 2009
                : 37
                : 17
                : e115
                Affiliations
                1Institute for Informatics, Ludwig-Maximilians-Universität München, Munich 80333 and 2Max von Pettenkofer-Institute, Ludwig-Maximilians-Universität München, Munich 80337, Germany
                Author notes
                *To whom correspondence should be addressed. Tel: +49-89-2180-4056; Fax: +49-89-2180-4054; Email: caroline.friedel@ 123456bio.ifi.lmu.de Correspondence may also be addressed to Dr Lars Dölken. Tel: +49-89-5160-5290; Fax: +49-89-5160-5292; Email: doelken@ 123456mvp.uni-muenchen.de

                The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.

                Article
                gkp542
                10.1093/nar/gkp542
                2761256
                19561200
                ea5e1d2c-2350-4306-9a10-25d1aaacac6a
                © 2009 The Author(s)

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 May 2009
                : 8 June 2009
                : 9 June 2009
                Categories
                Methods Online

                Genetics
                Genetics

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