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Gebauer F.,Center for Genomic Regulation and
Cold Spring Harbor perspectives in biology | Year: 2012

Messenger RNAs (mRNAs), the templates for translation, have evolved to harbor abundant cis-acting sequences that affect their posttranscriptional fates. These elements are frequently located in the untranslated regions and serve as binding sites for trans-acting factors, RNA-binding proteins, and/or small non-coding RNAs. This article provides a systematic synopsis of cis-acting elements, trans-acting factors, and the mechanisms by which they affect translation. It also highlights recent technical advances that have ushered in the era of transcriptome-wide studies of the ribonucleoprotein complexes formed by mRNAs and their trans-acting factors.

Lehner B.,Center for Genomic Regulation and | Lehner B.,Catalan Institution for Research and Advanced Studies
Nature Reviews Genetics | Year: 2013

To what extent can variation in phenotypic traits such as disease risk be accurately predicted in individuals? In this Review, I highlight recent studies in model organisms that are relevant both to the challenge of accurately predicting phenotypic variation from individual genome sequences ('whole-genome reverse genetics') and for understanding why, in many cases, this may be impossible. These studies argue that only by combining genetic knowledge with in vivo measurements of biological states will it be possible to make accurate genetic predictions for individual humans. © 2013 Macmillan Publishers Limited. All rights reserved.

Warnecke T.,Center for Genomic Regulation and
Molecular Biology and Evolution | Year: 2012

The DnaK-DnaJ-GrpE (KJE) chaperone system functions at the fulcrum of protein homeostasis in bacteria. It interacts both with nascent polypeptides and with proteins that have become unfolded, either funneling its clients toward the native state or ushering misfolded proteins into degradation. In line with its key role in protein folding, KJE has been considered an essential building block for a minimal bacterial genome and common to all bacteria. In this study, I present a rigorous survey of 1,233 bacterial genomes, which reveals that the entire KJE system is uniquely absent from two members of the order Aquificales, Desulfurobacterium thermolithotrophum, and Thermovibrio ammonificans. The absence of KJE from these free-living bacteria is surprising, particularly in light of the finding that individual losses of grpE and dnaJ are restricted to obligate endosymbionts with highly reduced genomes, whereas dnaK has never been lost in isolation. Examining protein features diagnostic of DnaK substrates in Escherichia coli, radical changes in protein solubility emerge as a likely precondition for the loss of KJE. Both D. thermolithotrophum and T. ammonificans grow under strictly anaerobic conditions at temperatures in excess of 70°C, reminiscent of hyperthermophilic archaea, which-unlike their mesophilic cousins-also lack KJE. I suggest that high temperature promotes the evolution of high intrinsic protein solubility on a proteome-wide scale and thereby creates conditions under which KJE can be lost. However, the shift in solubility is common to all Aquificales and hence not sufficient to explain the restricted incidence of KJE loss. © 2012 The Author.

Dessimoz C.,Swiss Institute of Bioinformatics | Gabaldon T.,Center for Genomic Regulation and | Roos D.S.,University of Pennsylvania | Sonnhammer E.L.L.,Stockholm Bioinformatics Center | Herrero J.,European Bioinformatics Institute
Bioinformatics | Year: 2012

The identification of orthologs-genes pairs descended from a common ancestor through speciation, rather than duplication-has emerged as an essential component of many bioinformatics applications, ranging from the annotation of new genomes to experimental target prioritization. Yet, the development and application of orthology inference methods is hampered by the lack of consensus on source proteomes, file formats and benchmarks. The second 'Quest for Orthologs' meeting brought together stakeholders from various communities to address these challenges. We report on achievements and outcomes of this meeting, focusing on topics of particular relevance to the research community at large. The Quest for Orthologs consortium is an open community that welcomes contributions from all researchers interested in orthology research and applications. © The Author(s) 2012. Published by Oxford University Press.

Campelo F.,Center for Genomic Regulation and | Malhotra V.,Center for Genomic Regulation and | Malhotra V.,Catalan Institution for Research and Advanced Studies
Annual Review of Biochemistry | Year: 2012

Membrane-bound transport carriers are used to transfer cargo between membranes of the secretory and the endocytic pathways. The generation of these carriers can be classified into three steps: segregation of cargo away from the residents of a donor compartment (cargo sorting), generation of membrane curvature commensurate with the size of the cargo (membrane budding or tubulation), and finally separation of the nascent carrier from the donor membrane by a scission or membrane fission event. This review summarizes advances in our understanding of some of the best-characterized proteins required for the membrane fission that separates a transport carrier from its progenitor compartment: the large GTPase dynamin, the small guanine nucleotide-binding (G) proteins of the Arf family, BAR (Bin-amphiphysin-Rvs) domain proteins, and protein kinase D. These proteins share their ability to insert into membranes and oligomerize to create the large curvatures; however, the overall process of fission that involves these proteins appears to be quite different. © 2012 by Annual Reviews. All rights reserved.

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