Abstract:
:Toscana virus (TOSV) is an arthropod-borne human pathogen responsible for seasonal outbreaks of fever and meningoencephalitis in the Mediterranean basin. TOSV is a segmented negative-strand RNA virus (sNSV) that belongs to the genus phlebovirus (family Phenuiviridae, order Bunyavirales), encompassing other important human pathogens such as Rift Valley fever virus (RVFV). Here, we carried out a structural and functional characterization of the TOSV cap-snatching endonuclease, an N terminal domain of the viral polymerase (L protein) that provides capped 3'OH primers for transcription. We report TOSV endonuclease crystal structures in the apo form, in complex with a di-ketoacid inhibitor (DPBA) and in an intermediate state of inhibitor release, showing details on substrate binding and active site dynamics. The structure reveals substantial folding rearrangements absent in previously reported cap-snatching endonucleases. These include the relocation of the N terminus and the appearance of new structural motifs important for transcription and replication. The enzyme shows high activity rates comparable to other His+ cap-snatching endonucleases. Moreover, the activity is dependent on conserved residues involved in metal ion and substrate binding. Altogether, these results bring new light on the structure and function of cap-snatching endonucleases and pave the way for the development of specific and broad-spectrum antivirals.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Jones R,Lessoued S,Meier K,Devignot S,Barata-García S,Mate M,Bragagnolo G,Weber F,Rosenthal M,Reguera Jdoi
10.1093/nar/gkz838subject
Has Abstractpub_date
2019-11-18 00:00:00pages
10914-10930issue
20eissn
0305-1048issn
1362-4962pii
5580917journal_volume
47pub_type
杂志文章abstract::G-quadruplexes are dynamic structures folded in G-rich single-stranded DNA regions. These structures have been recognized as a potential nucleic acid based mechanism for regulating multiple cellular processes such as replication, transcription and genomic maintenance. So far, their transcriptional role in vivo during ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw011
更新日期:2016-05-19 00:00:00
abstract::The Génolevures online database (http://cbi.labri.fr/Genolevures/ and http://genolevures.org/) provides exploratory tools and curated data sets relative to nine complete and seven partial genome sequences determined and manually annotated by the Génolevures Consortium, to facilitate comparative genomic studies of Hemi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn859
更新日期:2009-01-01 00:00:00
abstract::Approaches to characterize the nucleic acid-binding properties of drugs and druglike small molecules are crucial to understanding the behavior of these compounds in cellular systems. Here, we use a Small Molecule Microarray (SMM) profiling approach to identify the preferential interaction between chlorhexidine, a wide...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky084
更新日期:2018-04-06 00:00:00
abstract::Autosomal dominant and/or recessive progressive external ophthalmoplegia (ad/arPEO) is associated with mtDNA mutagenesis. It can be caused by mutations in three nuclear genes, encoding the adenine nucleotide translocator 1, the mitochondrial helicase Twinkle or DNA polymerase gamma (POLG). How mutations in these genes...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh634
更新日期:2004-06-04 00:00:00
abstract::We have determined the nucleotide sequence at the 3' end of the vesicular stomatitis virus (VSV) polymerase or L gene and compared it to that obtained from a defective interfering particle (DI) RNA generated by this virus. The latter (DI 0.50) contains a large internal deletion within this gene. The deletion begins ex...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/10.21.6919
更新日期:1982-11-11 00:00:00
abstract::Inducible promoters are a central regulatory component in synthetic biology, metabolic engineering, and protein production for laboratory and commercial uses. Many of these applications utilize two or more exogenous promoters, imposing a currently unquantifiable metabolic burden on the living system. Here, we engineer...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa734
更新日期:2020-09-25 00:00:00
abstract::Rad18 is a ubiquitin E3 ligase that monoubiquitinates PCNA on stalled replications forks. This allows recruitment of damage-tolerant polymerases for damage bypass and DNA repair. In this activity, the Rad18 protein has to interact with Rad6, the E2 ubiquitin-conjugating enzyme, ubiquitin, PCNA and DNA. Here we analyze...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm615
更新日期:2007-01-01 00:00:00
abstract::Insertion of microRNA target sequences into the flavivirus genome results in selective tissue-specific attenuation and host-range restriction of live attenuated vaccine viruses. However, previous strategies for miRNA-targeting did not incorporate a mechanism to prevent target elimination under miRNA-mediated selective...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw061
更新日期:2016-04-20 00:00:00
abstract::A set of programs was developed for searching nucleic acid and protein sequence data bases for sequences similar to a given sequence. The programs, written in FORTRAN 77, were optimized for vector processing on a Hitachi S810-20 supercomputer. A search of a 500-residue protein sequence against the entire PIR data base...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/14.1.57
更新日期:1986-01-10 00:00:00
abstract::Controllable gene delivery via vector-based systems remains a formidable challenge in mammalian synthetic biology and a desirable asset in gene therapy applications. Here, we introduce a methodology to control the copies and residence time of a gene product delivered in host human cells but also selectively disrupt fr...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gku1326
更新日期:2015-01-01 00:00:00
abstract::Sequencing by hybridization (SBH) approaches to DNA sequencing face two conflicting constraints. First, in order to ensure that the target DNA binds reliably, the oligonucleotide probes that are attached to the chip array must be >15 bp in length. Secondly, the total number of possible 15 bp oligonucleotides is too la...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh210
更新日期:2004-02-18 00:00:00
abstract::Cells deficient in the Werner syndrome protein (WRN) or BRCA1 are hypersensitive to DNA interstrand cross-links (ICLs), whose repair requires nucleotide excision repair (NER) and homologous recombination (HR). However, the roles of WRN and BRCA1 in the repair of DNA ICLs are not understood and the molecular mechanisms...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl362
更新日期:2006-05-19 00:00:00
abstract::Chromatin organization and epigenetic markers influence splicing, though the magnitudes of these effects and the mechanisms are largely unknown. Here, we demonstrate that linker histone H1.5 influences mRNA splicing. We observed that linker histone H1.5 binds DNA over splice sites of short exons in human lung fibrobla...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz338
更新日期:2019-07-09 00:00:00
abstract::To examine the influence of thyrotropin (TSH) on the thyroglobulin (Tgb) mRNA content, the latter was evaluated in the cytoplasm of hog thyroid cells cultured in the absence (control cells) or presence of TSH. The Tgb mRNA levels were determined by, (i) kinetics of hybridization to sheep Tgb cDNA, (ii) capacity of cod...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/6.10.3353
更新日期:1979-07-25 00:00:00
abstract::Gel migration and uranyl photoprobing have been used to study the effects of inosine and 2,6-diaminopurine (2,6-DAP) substitution on adenine-tract (A-tract) induced DNA curvature. Using a 10mer repeated sequence including five inosines we show by uranyl photoprobing that a narrow minor groove varying in phase with the...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/25.17.3497
更新日期:1997-09-01 00:00:00
abstract::As protein-protein interactions are crucial in most biological processes, it is valuable to understand how and where protein pairs interact. We developed a web server HOMCOS (Homology Modeling of Complex Structure, http://biunit.naist.jp/homcos) to predict interacting protein pairs and interacting sites by homology mo...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn218
更新日期:2008-07-01 00:00:00
abstract::Labeling of a covalently closed circular double-stranded DNA was achieved using a so-called 'padlock oligonucleotide'. The oligonucleotide was targeted to a sequence which is present in the replication origin of phage f1 and thus in numerous commonly used plasmids. After winding around the double-stranded target DNA s...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/30.3.e12
更新日期:2002-02-01 00:00:00
abstract::Essential genes are genes that are indispensable to support cellular life. These genes constitute a minimal gene set required for a living cell. We have constructed a Database of Essential Genes (DEG), which contains all the essential genes that are currently available. The functions encoded by essential genes are con...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh024
更新日期:2004-01-01 00:00:00
abstract::Increasing numbers of proteins, nucleic acids and other molecular entities have been explored as therapeutic targets, hundreds of which are targets of approved and clinical trial drugs. Knowledge of these targets and corresponding drugs, particularly those in clinical uses and trials, is highly useful for facilitating...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp1014
更新日期:2010-01-01 00:00:00
abstract::Ribosomal protein (RP) genes must be coordinately expressed for proper assembly of the ribosome yet the mechanisms that control expression of RP genes in metazoans are poorly understood. Recently, TATA-binding protein-related factor 2 (TRF2) rather than the TATA-binding protein (TBP) was found to function in transcrip...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx676
更新日期:2017-10-13 00:00:00
abstract::The DNA Data Bank of Japan (DDBJ) (http://www.ddbj.nig.ac.jp) has been providing public data services for thirty years (since 1987). We are collecting nucleotide sequence data from researchers as a member of the International Nucleotide Sequence Database Collaboration (INSDC, http://www.insdc.org), in collaboration wi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw1001
更新日期:2017-01-04 00:00:00
abstract::Module identification is a frequently used approach for mining local structures with more significance in global networks. Recently, a wide variety of bilayer networks are emerging to characterize the more complex biological processes. In the light of special topological properties of bilayer networks and the accompan...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw679
更新日期:2016-11-16 00:00:00
abstract::Using cyanoethyldiisopropylamino phosphoramidite chemistry, four oligonucleotides constituting a part of the sequence of the initiator t-RNA from B. subtilis were synthesized. For the protection of the exocyclic amino functions of bases, phenoxyacetyl group was used for adenine and guanine, and acetyl group was prefer...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/17.18.7381
更新日期:1989-09-25 00:00:00
abstract::PDB-REPRDB is a database of representative protein chains from the Protein Data Bank (PDB). Started at the Real World Computing Partnership (RWCP) in August 1997, it developed to the present system of PDB-REPRDB. In April 2001, the system was moved to the Computational Biology Research Center (CBRC), National Institut...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkg022
更新日期:2003-01-01 00:00:00
abstract::Neuroserpin is an axonally secreted serine protease inhibitor expressed in the nervous system that protects neurons from ischemia-induced apoptosis. Mutant neuroserpin forms have been found polymerized in inclusion bodies in a familial autosomal encephalopathy causing dementia, or associated with epilepsy. Regulation ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/30.10.2202
更新日期:2002-05-15 00:00:00
abstract::Stability of aromatic phosphoramidates was studied using 2',3'-O-dibenzoyluridine 5'-phosphoramidates and N,2',3'-O-tribenzoylcytidine 5'-phosphate. The effect of dicyclohexylcarbodiimide in this mixture was investigated. Decomposition of the anilidate was slower in the presence of DCC. Substituted anilidates of uridi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/1.2.223
更新日期:1974-02-01 00:00:00
abstract::Human immunodeficiency virus type 2 (HIV-2) reverse transcription is initiated from cellular tRNA(Lys3) partially annealed to the RNA viral genome at the primer binding site (PBS). This annealing involves interactions between two highly structured RNA molecules. In contrast to HIV-1, in which the reverse transcription...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.13.2757
更新日期:2001-07-01 00:00:00
abstract::By in vivo DMS footprint and reporter gene analyses we identified two transcription factor binding sites in the human c-sis/PDGF B gene promoter. The low basal activity of the PDGF B promoter in HeLa and undifferentiated K562 cells, which express low PDGF B mRNA levels, and in PC3 cells, which express a high PDGF B mR...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/23.7.1119
更新日期:1995-04-11 00:00:00
abstract::The major mRNA degradation pathway involves deadenylation of the target molecule followed by decapping and, finally, 5'-->3' exonuclease digestion of the mRNA body. While yeast factors involved in the decapping and exonuclease degradation steps have been identified, the nature of the factor(s) involved in the deadenyl...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.12.2448
更新日期:2001-06-15 00:00:00
abstract::Interleukin 2 (IL2) mRNA has a short half-life in the cytoplasm of T lymphocytes, relative to most mRNA. We have discovered a candidate ribonuclease to account for the rapid turnover of IL2 mRNA in the cytosol of the human T lymphocyte cell line Jurkat. In partially purified form, this RNase is about 7 times as active...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.1.155
更新日期:1993-01-11 00:00:00