Biology subjects

Bateman, A.

Publications and source records attributed to Bateman, A..

24 records · Page 2Linked to original sources

bioRxiv2019

Caenorhabditis elegans AF4/FMR2 family homolog affl-2 is required for heat shock induced gene expression

To mitigate the deleterious effects of temperature increases on cellular organization and proteotoxicity, organisms have developed mechanisms to respond to heat stress. In eukaryotes, HSF1 is the master regulator of the heat shock transcriptional response, but the heat shock response pathway is not yet fully understood. From a forward genetic screen for suppressors of heat shock induced gene expression in C. elegans, we identified a new allele of hsf-1 that alters its DNA-binding domain, and three additional alleles of sup-45, a previously uncharacterized genetic locus. We identified sup-45 as one of the two hitherto unknown C. elegans orthologs of the human AF4/FMR2 family proteins, which are involved in regulation of transcriptional elongation rate. We thus renamed sup-45 as affl-2 (AF4/FMR2-Like). affl-2 mutants are egg-laying defective and dumpy, but worms lacking its sole paralog (affl-1) appear wild-type. AFFL-2 is a broadly expressed nuclear protein, and nuclear localization of AFFL-2 is necessary for its role in heat shock response. affl-2 and its paralog are not essential for proper HSF-1 expression and localization after heat shock, which suggests that affl-2 may function downstream or parallel of hsf-1. Our characterization of affl-2 provides insights into the complex processes of transcriptional elongation and regulating heat shock induced gene expression to protect against heat stress.

genetics↗

bioRxiv2019

Thrombospondin module 1 domain (TSP1) of the matricellular protein CCN3 shows an atypical disulfide pattern and incomplete CWR layers

Members of the CCN (Cyr61/CTGF/Nov) family are a group of matricellular regulatory proteins, essential to a wide range of functional pathways in cell signalling. Through interacting with extracellular matrix components and growth factors via one of its four domains, the CCN proteins are involved in critical biological processes such as angiogenesis, cell proliferation, bone development, fibrogenesis, and tumorigenesis. We present here the crystal structure of the thrombospondin module 1 (TSP1) domain of CCN3 (previously known as Nov), which shares a similar three-stranded fold with the thrombospondin type 1 repeats of thrombospondin-1 and Spondin-1, but with variations in the disulfide connectivity. Moreover, the CCN3 TSP1 lacks the typical pi-stacked ladder of charged and aromatic residues on one side of the domain, as seen in other TSP1 domains. Using conservation analysis among orthologous domains, we show that a charged cluster in the centre of the domain is the most conserved site and predict it to be a potential functional epitope for heparan sulphate binding. This variant TSP1 domain has also been used to revise the sequence determinants of TSP1 domains and derive improved Pfam sequence profiles for identification of novel TSP1 domains in more than 10,000 proteins across diverse phyla.\n\nSynopsisThe first structure of a thrombospondin module 1 domain (TSP1) from a CCN family matricellular protein has been determined by X-ray crystallography. The structure shows a typical three-stranded fold, but with an incomplete pi-stacked structure that is usually found in these domains. The structure reveals highest conservation in the positively charged central segment, which we predict to be a binding site for heparan sulphates. The atypical features of this domain have been used to revise the definition of the TSP1 domains and identify a number of new domains in sequence databases.

biochemistry↗

bioRxiv2019

Sequence analysis allows functional annotation of tyrosine recombinases in prokaryotic genomes

BackgroundTyrosine recombinases perform site-specific genetic recombination in bacteria and archaea. They safeguard genome integrity by resolving chromosome multimers, as well as mobilize transposons, phages and integrons, driving dissemination of genetic traits and antibiotic resistance. Despite their abundance and genetic impact, tyrosine recombinase diversity and evolution has not been thoroughly characterized, which greatly hampers their functional classification. ResultsHere, we conducted a comprehensive search and comparative analysis of diverse tyrosine recombinases from bacterial, archaeal and phage genomes. We characterized their major phylogenetic groups and show that recombinases of integrons and insertion sequences are closely related to the chromosomal Xer proteins, while integrases of integrative and conjugative elements (ICEs) and phages are more distant. We find that proteins in distinct phylogenetic groups share specific structural features and have characteristic taxonomic distribution. We further trace tyrosine recombinase evolution and propose that phage and ICE integrases originated by acquisition of an N-terminal arm-binding domain. Based on this phylogeny, we classify numerous known ICEs and predict new ones. ConclusionsThis work provides a new resource for comparative analysis and functional annotation of tyrosine recombinases. We reconstitute protein evolution and show that adaptation for a role in gene transfer involved acquisition of a specific protein domain, which allows precise regulation of excision and integration.

evolutionary biology↗

bioRxiv2018

The Human RNA-Binding Proteome and Its Dynamics During Arsenite-Induced Translational Arrest

Proteins and RNA functionally and physically intersect in multiple biological processes, however, currently no universal method is available to purify protein-RNA complexes. Here we introduce XRNAX, a method for the generic purification of protein-crosslinked RNA, and demonstrate its versatility to study the composition and dynamics of protein-RNA interactions by various transcriptomic and proteomic approaches. We show that XRNAX captures all RNA biotypes, and use this to characterize the sub-proteomes that interact with coding and non-coding RNAs (ncRNAs), and to identify hundreds of protein-RNA interfaces. Exploiting the quantitative nature of XRNAX, we observe drastic remodeling of the RNA-bound proteome during arsenite-induced stress, distinct from autophagy-induced changes in the total proteome. In addition, we combine XRNAX with CLIP-seq to validate the interaction of ncRNA with Lamin B and EXOSC2. Thus, XRNAX is a resourceful approach to study structural and compositional aspects of protein-RNA interactions to address fundamental questions in RNA-biology.

molecular biology↗

bioRxiv2017

TOWARDS A GLOBAL SUPPORT OF CORE DATA RESOURCES FOR THE LIFE SCIENCES

On November 18-19, 2016, the Human Frontier Science Program Organization (HFSPO) hosted a meeting of senior managers of key data resources and leaders of several major funding organizations to discuss the challenges associated with sustaining biological and biomedical (i.e., life sciences) data resources and associated infrastructure. A strong consensus emerged from the group that core data resources for the life sciences should be supported through a coordinated international effort(s) that better ensure long-term sustainability and that appropriately align funding with scientific impact. Ideally, funding for such data resources should allow for access at no charge, as is presently the usual (and preferred) mechanism. Below, the rationale for this vision is described, and some important considerations for developing a new international funding model to support core data resources for the life sciences are presented.

scientific communication and education↗

bioRxiv2016

On expert curation and sustainability: UniProtKB/Swiss-Prot as a case study

MOTIVATIONBiological knowledgebases, such as UniProtKB/Swiss-Prot, constitute an essential component of daily scientific research by offering distilled, summarized, and computable knowledge extracted from the literature by expert curators. While knowledgebases play an increasingly important role in the scientific community, the question of their sustainability is raised due to the growth of biomedical literature.\n\nRESULTSBy using UniProtKB/Swiss-Prot as a case study, we address this question by using different literature triage approaches. With the assistance of the PubTator text-mining tool, we tagged more than 10,000 articles to assess the ratio of papers relevant for curation. We first show that curators read and evaluate many more papers than they curate, and that measuring the number of curated publications is insufficient to provide a complete picture. We show that a large fraction of published papers found in PubMed is not relevant for curation in UniProtKB/Swiss-Prot and demonstrate that, despite appearances, expert curation is sustainable.\n\nAVAILABILITYUniProt is freely available at http://www.uniprot.org/.\n\nCONTACTsylvain.poux@sib.swiss

bioinformatics↗