Abstract:
:The current pandemic situation caused by the Betacoronavirus SARS-CoV-2 (SCoV2) highlights the need for coordinated research to combat COVID-19. A particularly important aspect is the development of medication. In addition to viral proteins, structured RNA elements represent a potent alternative as drug targets. The search for drugs that target RNA requires their high-resolution structural characterization. Using nuclear magnetic resonance (NMR) spectroscopy, a worldwide consortium of NMR researchers aims to characterize potential RNA drug targets of SCoV2. Here, we report the characterization of 15 conserved RNA elements located at the 5' end, the ribosomal frameshift segment and the 3'-untranslated region (3'-UTR) of the SCoV2 genome, their large-scale production and NMR-based secondary structure determination. The NMR data are corroborated with secondary structure probing by DMS footprinting experiments. The close agreement of NMR secondary structure determination of isolated RNA elements with DMS footprinting and NMR performed on larger RNA regions shows that the secondary structure elements fold independently. The NMR data reported here provide the basis for NMR investigations of RNA function, RNA interactions with viral and host proteins and screening campaigns to identify potential RNA binders for pharmaceutical intervention.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Wacker A,Weigand JE,Akabayov SR,Altincekic N,Bains JK,Banijamali E,Binas O,Castillo-Martinez J,Cetiner E,Ceylan B,Chiu LY,Davila-Calderon J,Dhamotharan K,Duchardt-Ferner E,Ferner J,Frydman L,Fürtig B,Gallego J,Grün JTdoi
10.1093/nar/gkaa1013subject
Has Abstractpub_date
2020-12-16 00:00:00pages
12415-12435issue
22eissn
0305-1048issn
1362-4962pii
5961789journal_volume
48pub_type
杂志文章abstract::Antisense oligodeoxynucleotides (ODNs) have biological activity in treating various forms of cancer. The antisense effects of two types of 20mer ODNs, phosphorothioate-modified ODNs (S-ODNs) and S-ODNs with 12 2'-O-methyl groups (Me-S-ODNs), targeted to sites 109 and 277 of bcl-2 mRNA, were compared. Both types were a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh516
更新日期:2004-04-02 00:00:00
abstract::The ability to sense and respond to environmental and physiological signals is critical for the survival of the soil-dwelling Gram-positive bacterium Streptomyces coelicolor. Nutrient deprivation triggers the onset of a complex morphological differentiation process that involves the raising of aerial hyphae and format...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm1096
更新日期:2008-02-01 00:00:00
abstract::The template requirements for efficient adenovirus DNA replication were studied in vitro in a reconstituted system with cloned DNA fragments, containing the Ad2 origin region, as templates. Replication is enhanced by nuclear factor I, a cellular protein that binds specifically to the Ad2 origin. This stimulation is sh...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/13.13.4935
更新日期:1985-07-11 00:00:00
abstract::According to recent models, as yet poorly studied architectural proteins appear to be required for local regulation of enhancer-promoter interactions, as well as for global chromosome organization. Transcription factors ZIPIC, Pita and Zw5 belong to the class of chromatin insulator proteins and preferentially bind to ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw371
更新日期:2016-09-06 00:00:00
abstract::MicroRNAs are small non-coding RNAs that modulate gene expression at post-transcriptional level, playing a crucial role in cell differentiation and development. Recently, some reports have shown that a limited number of mammalian microRNAs are also involved in anti-viral defense. In this study, the analysis of the hep...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr067
更新日期:2011-07-01 00:00:00
abstract::RNA molecules play different roles in coding, decoding and gene expression regulation. Such roles are often associated to the RNA secondary or tertiary structures. The folding dynamics lead to multiple secondary structures of long RNA molecules, since an RNA molecule might fold into multiple distinct native states. De...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gku1249
更新日期:2014-12-16 00:00:00
abstract::Bisulfite genomic sequencing is the most widely used technique to analyze the 5-methylation of cytosines, the prevalent covalent DNA modification in mammals. The process is based on the selective transformation of unmethylated cytosines to uridines. Then, the investigated genomic regions are PCR amplified, subcloned a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gni012
更新日期:2005-01-13 00:00:00
abstract::The multifunctional HCV core protein consists of a hydrophilic RNA interacting D1 domain and a hydrophobic D2 domain interacting with membranes and lipid droplets. The core D1 domain was found to possess nucleic acid annealing and strand transfer properties. To further understand these chaperone properties, we investi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq094
更新日期:2010-06-01 00:00:00
abstract::Motif3D is a web-based protein structure viewer designed to allow sequence motifs, and in particular those contained in the fingerprints of the PRINTS database, to be visualised on three-dimensional (3D) structures. Additional functionality is provided for the rhodopsin-like G protein-coupled receptors, enabling finge...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkg534
更新日期:2003-07-01 00:00:00
abstract::U1 snRNP plays a crucial role in the 5' splice site recognition during splicing. Here we report the first example of naturally occurring U1-independent U2-type splicing in humans. The U1 components were not included in the pre-spliceosomal E complex formed on the human F1gamma (hF1gamma) intron 9 in vitro. Moreover, h...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp050
更新日期:2009-04-01 00:00:00
abstract::Triantennary N-acetyl galactosamine (GalNAc, GN3: ), a high-affinity ligand for the hepatocyte-specific asialoglycoprotein receptor (ASGPR), enhances the potency of second-generation gapmer antisense oligonucleotides (ASOs) 6-10-fold in mouse liver. When combined with next-generation ASO designs comprised of short S-c...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gku531
更新日期:2014-07-01 00:00:00
abstract::Methylation of CpG motifs in DNA is involved in the control of gene expression and in several other epigenic effects. It suppresses also the immuno-stimulation properties of bacterial or viral DNAs that contain CPGS: However, effects of methylation on the DNA structure and dynamics are not clear. Here we carried out a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.11.2314
更新日期:2001-06-01 00:00:00
abstract::The DNA double helix undergoes an 'overstretching' transition in a narrow force range near 65 pN. Despite numerous studies the basic question of whether the strands are separated or not remains controversial. Here we show that overstretching in fact involves two distinct types of double-helix reorganization: slow hyst...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq309
更新日期:2010-09-01 00:00:00
abstract::We report the extended database and data mining resources newly released in the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). H-InvDB is a comprehensive annotation resource of human genes and transcripts, and consists of two main views and six sub-databases. The latest release of H-InvDB (release 6...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp1020
更新日期:2010-01-01 00:00:00
abstract::Recently published alignments of available 5 S rRNA sequences have shown that a rigid base pairing pattern, pointing to the existence of a universal five-helix secondary structure for all 5 S RNAs, can be superimposed on such alignments. For a few species, the alignment and the base pairing pattern show distortions wi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/11.5.1245
更新日期:1983-03-11 00:00:00
abstract::MicroRNAs (miRNA) are short single-stranded RNA molecules derived from hairpin-forming precursors that play a crucial role as post-transcriptional regulators in eukaryotes and viruses. In the past years, many microRNA target genes (MTGs) have been identified experimentally. However, because of the high costs of experi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw1085
更新日期:2017-01-25 00:00:00
abstract::TFIIH is a multisubunit factor essential for transcription initiation and promoter escape of RNA polymerase II and for the opening of damaged DNA double strands in nucleotide excision repair (NER). In this study, we have analyzed at which step of the transcription cycle TFIIH is essential for transcription by RNA poly...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr746
更新日期:2012-01-01 00:00:00
abstract::Archaeal family-B DNA polymerases bind tightly to deaminated bases and stall replication on encountering uracil in template strands, four bases ahead of the primer-template junction. Should the polymerase progress further towards the uracil, for example, to position uracil only two bases in front of the junction, 3'-5...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks1364
更新日期:2013-02-01 00:00:00
abstract::DNA helicases are required for virtually every aspect of DNA metabolism, including replication, repair, recombination and transcription. A comprehensive description of these essential biochemical processes requires detailed understanding of helicase mechanisms. These enzymes are ubiquitous, having been identified in v...
journal_title:Nucleic acids research
pub_type: 杂志文章,评审
doi:10.1093/nar/gkl501
更新日期:2006-01-01 00:00:00
abstract::While it has been long recognized that genes are not randomly positioned along the genome, the degree to which its 3D structure influences the arrangement of genes has remained elusive. In particular, several lines of evidence suggest that actively transcribed genes are spatially co-localized, forming transcription fa...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks1360
更新日期:2013-02-01 00:00:00
abstract::The smallest catalytic RNA identified to date is a manganese-dependent ribozyme that requires only a complex between GAAA and UUU to effect site-specific cleavage. We show here that this ribozyme occurs naturally in the 3'-UTR of Vg1 and beta-actin mRNAs. In accord with earlier studies with model RNAs, cleavage occurs...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn530
更新日期:2008-10-01 00:00:00
abstract::RNA is emerging as a key regulator of a plethora of biological processes. While its study has remained elusive for decades, the recent advent of high-throughput sequencing technologies provided the unique opportunity to develop novel techniques for the study of RNA structure and post-transcriptional modifications. Non...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky486
更新日期:2018-09-19 00:00:00
abstract::1731, a Drosophila retrotransposon was first described as having a transcription activity which was negatively regulated by 20-hydroxyecdysone (20-OH), the steroid molting hormone of insects. Using constructions expressing the bacterial chloramphenicol-acetyltransferase (CAT) gene under the control of the entire or de...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/19.20.5689
更新日期:1991-10-25 00:00:00
abstract::Preparation of the two nonanucleotides, d(pG-G-A-G-G-A-G-A-A) and d(pT-T-C-T-G-T-T-G-A), and the octanucleotide, d(pT-G-G-C-C-C-A-T) is described by a rapid solid-phase method on a polyamide support. The syntheses were carried out using a modified solid-phase peptide synthesiser and required one day for each nucleotid...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/4.12.4391
更新日期:1977-12-01 00:00:00
abstract::Reconstructing full-length transcript isoforms from sequence fragments (such as ESTs) is a major interest and challenge for bioinformatic analysis of pre-mRNA alternative splicing. This problem has been formulated as finding traversals across the splice graph, which is a directed acyclic graph (DAG) representation of ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl396
更新日期:2006-06-06 00:00:00
abstract::ComplexContact (http://raptorx2.uchicago.edu/ComplexContact/) is a web server for sequence-based interfacial residue-residue contact prediction of a putative protein complex. Interfacial residue-residue contacts are critical for understanding how proteins form complex and interact at residue level. When receiving a pa...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky420
更新日期:2018-07-02 00:00:00
abstract::Transcription of ribosomal RNA genes is generally accepted to correlate with cell growth. Using primary cultures of adult bovine aortic endothelial (ABAE) cells, we have shown that transcription of rDNA in confluent cells falls to 5% of the transcription level in growing cells. Protein kinase NII appears to be a limit...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/17.16.6625
更新日期:1989-08-25 00:00:00
abstract::It has been shown that the monomethylated cap structure plays important roles in pre-mRNA splicing and nuclear export of RNA. As a candidate for the factor involved in these nuclear events we have previously purified an 80 kDa nuclear cap binding protein (NCBP) from a HeLa cell nuclear extract and isolated its full-le...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/23.18.3638
更新日期:1995-09-25 00:00:00
abstract::Explicit solvent molecular dynamics (MD) was used to describe the intrinsic flexibility of the helix 42-44 portion of the 23S rRNA (abbreviated as Kt-42+rGAC; kink-turn 42 and GTPase-associated center rRNA). The bottom part of this molecule consists of alternating rigid and flexible segments. The first flexible segmen...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm245
更新日期:2007-01-01 00:00:00
abstract::Although cis-regulatory binding sites (CRBSs) are at least as important as the coding sequences in a genome, our general understanding of them in most sequenced genomes is very limited due to the lack of efficient and accurate experimental and computational methods for their characterization, which has largely hindere...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp248
更新日期:2009-06-01 00:00:00