Abstract:
:Prokaryotes use primed CRISPR adaptation to update their memory bank of spacers against invading genetic elements that have escaped CRISPR interference through mutations in their protospacer target site. We previously observed a trend that nucleotide-dependent mismatches between crRNA and the protospacer strongly influence the efficiency of primed CRISPR adaptation. Here we show that guanine-substitutions in the target strand of the protospacer are highly detrimental to CRISPR interference and interference-dependent priming, while cytosine-substitutions are more readily tolerated. Furthermore, we show that this effect is based on strongly decreased binding affinity of the effector complex Cascade for guanine-mismatched targets, while cytosine-mismatched targets only minimally affect target DNA binding. Structural modeling of Cascade-bound targets with mismatches shows that steric clashes of mismatched guanines lead to unfavorable conformations of the RNA-DNA duplex. This effect has strong implications for the natural selection of target site mutations that lead to effective escape from type I CRISPR-Cas systems.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Künne T,Zhu Y,da Silva F,Konstantinides N,McKenzie RE,Jackson RN,Brouns SJdoi
10.1093/nar/gky687subject
Has Abstractpub_date
2018-11-02 00:00:00pages
10395-10404issue
19eissn
0305-1048issn
1362-4962pii
5070486journal_volume
46pub_type
杂志文章abstract::Alternative splicing of pre-mRNA generates protein diversity. Dysfunction of splicing machinery and expression of specific transcripts has been linked to cancer progression and drug response. Exon microarray technology enables genome-wide quantification of expression levels of the majority of exons and facilitates the...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr513
更新日期:2011-10-01 00:00:00
abstract::The model mRNA (MR), 11-mer RNA containing two nitroxide spin labels at the 5'- and 3'-terminal nucleotides and prone to form a stable homodimer (MR)2, was used for Electron Paramagnetic Resonance study of structural rearrangements in mRNA occurring upon its binding to human 80S ribosomes. The formation of two differe...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx1136
更新日期:2018-01-25 00:00:00
abstract::The HAMSTeRS WWW site was set up in 1996 in order to facilitate easy access to, and aid understanding of, the causes of haemophilia A at the molecular level; previously, the first and second text editions of the database have been published in Nucleic Acids Research. This report describes the facilities originally ava...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/25.1.128
更新日期:1997-01-01 00:00:00
abstract::The Bovine Genome Database (BGD; http://BovineGenome.org) strives to improve annotation of the bovine genome and to integrate the genome sequence with other genomics data. BGD includes GBrowse genome browsers, the Apollo Annotation Editor, a quantitative trait loci (QTL) viewer, BLAST databases and gene pages. Genome ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq1235
更新日期:2011-01-01 00:00:00
abstract::ATR functions as a master regulator of the DNA-damage response. ATR activation requires the ATR activator, topoisomerase IIβ-binding protein 1 (TopBP1). However, the underlying mechanism of TopBP1 regulation and how its regulation affects DNA replication remain unknown. Here, we report a specific interaction between T...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa756
更新日期:2020-11-04 00:00:00
abstract::DNA polymerase beta (polbeta), a member of the X family of DNA polymerases, is the major polymerase in the base excision repair pathway. Using in vitro selection, we obtained RNA aptamers for polbeta from a variable pool of 8 x 10(12) individual RNA sequences containing 30 random nucleotides. A total of 60 individual ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl326
更新日期:2006-05-17 00:00:00
abstract::The CATH database of protein domain structures (http://www.biochem.ucl.ac.uk/bsm/cath_new) currently contains 34 287 domain structures classified into 1383 superfamilies and 3285 sequence families. Each structural family is expanded with domain sequence relatives recruited from GenBank using a variety of efficient seq...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkg062
更新日期:2003-01-01 00:00:00
abstract::The genomic distribution of 23 nuclear genes from three dicotyledons (pea, sunflower, tobacco) and five monocotyledons of the Gramineae family (barley, maize, rice, oat, wheat) was studied by localizing these genes in DNA fractions obtained by preparative centrifugation in Cs2SO4/BAMD density gradients. Each one of th...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/18.7.1859
更新日期:1990-04-11 00:00:00
abstract::Messenger RNA in eukaryotes is comprised of several abundance classes. Also, the decay of these unstable molecules shows at least two very different lifetimes. Two independent techniques are used here to examine the relation between message abundance and lifetime in cell lines from very different organisms. The method...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/5.8.3057
更新日期:1978-08-01 00:00:00
abstract::Major efforts are underway to elucidate the spatial distribution of ribosomal RNAs (rRNAs) in the ribosome. An especially informative approach is the identification of likely base-base tertiary interactions within the RNA by phylogenetic comparison. Herein evidence is presented for three heretofore unrecognized candid...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/17.6.2215
更新日期:1989-03-25 00:00:00
abstract::Targeted differentiation of human induced pluripotent stem cells (hiPSCs) using only chemicals would have value-added clinical potential in the regeneration of complex cell types including cardiomyocytes. Despite the availability of several chemical inhibitors targeting proteins involved in signaling pathways, no bioa...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx693
更新日期:2017-09-19 00:00:00
abstract::Embryonic stem cells (ESCs) and meiosis are featured by relatively higher frequent homologous recombination associated with DNA double strand breaks (DSB) repair. Here, we show that Pold3 plays important roles in DSB repair, telomere maintenance and genomic stability of both ESCs and spermatocytes in mice. By attempti...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky098
更新日期:2018-04-20 00:00:00
abstract::The vertebrate genome is a mosaic of regions differing dramatically in their G + C content. Those regions with a high G + C content contain the expected number of CpG dinucleotides and we propose that following methylation these have been protected from deamination by the increased stability of the surrounding DNA dup...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/12.14.5869
更新日期:1984-07-25 00:00:00
abstract::Alu insertions have contributed to >11% of the human genome and ∼30-35 Alu subfamilies remain actively mobile, yet the characterization of polymorphic Alu insertions from short-read data remains a challenge. We build on existing computational methods to combine Alu detection and de novo assembly of WGS data as a means...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv1089
更新日期:2015-12-02 00:00:00
abstract::LINE-1 (L1) is a highly successful autonomous non-LTR retrotransposon and a major force shaping mammalian genomes. Although there are about 600 000 L1 copies covering 23% of the rat genome, full-length rat L1s (L1Rn) with intact open reading frames (ORFs) representing functional master copies for retrotransposition ha...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm1045
更新日期:2008-02-01 00:00:00
abstract::Human Adenovirus type 5 encodes two short RNA polymerase III transcripts, the virus-associated (VA) RNAI and VA RNAII, which can adopt stable hairpin structures that resemble micro-RNA precursors. The terminal stems of the VA RNAs are processed into small RNAs (mivaRNAs) that are incorporated into RISC. It has been re...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp764
更新日期:2009-11-01 00:00:00
abstract::To understand the epigenetic regulation of transcriptional response of macrophages during early-stage M. tuberculosis (Mtb) infection, we performed ChIPseq analysis of H3K4 monomethylation (H3K4me1), a marker of poised or active enhancers. De novo H3K4me1 peaks in infected cells were associated with genes implicated i...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw782
更新日期:2016-12-15 00:00:00
abstract::Proteins interacting with pre-mRNAs during early stages of spliceosome formation in a HeLa nuclear extract were investigated by photochemical RNA-protein crosslinking. The level of protein crosslinking to a beta-globin pre-mRNA was positively correlated with the presence of an intron. Proteins of 110,000, 59,000 and 3...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/18.11.3307
更新日期:1990-06-11 00:00:00
abstract::eIF4E-binding proteins (4E-BPs) regulate translation of mRNAs in eukaryotes. However the extent to which specific mRNA targets are regulated by 4E-BPs remains unknown. We performed translational profiling by microarray analysis of polysome and monosome associated mRNAs in wild-type and mutant cells to identify mRNAs i...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq686
更新日期:2010-12-01 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
abstract::PIR-International is an association of macromolecular sequence data collection centers dedicated to fostering international cooperation as an essential element in the development of scientific databases. A major objective of PIR-International is to continue the development of the Protein Sequence Database as an essent...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract::Pathogenic bacteria encounter host-imposed manganese (Mn) limitation during infection. Herein we report that in the human pathogen Streptococcus pyogenes, the adaptive response to Mn limitation is controlled by a DtxR family metalloregulator, MtsR. Genes upregulated by MtsR during Mn limitation include Mn (mtsABC) and...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz524
更新日期:2019-08-22 00:00:00
abstract::Understanding interactions between proteins and RNA is key to deciphering the mechanisms of many important biological processes. Here we describe RNABindR, a web-based server that identifies and displays RNA-binding residues in known protein-RNA complexes and predicts RNA-binding residues in proteins of unknown struct...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm294
更新日期:2007-07-01 00:00:00
abstract::Restriction endonuclease Bse634I recognizes and cleaves the degenerate DNA sequence 5'-R/CCGGY-3' (R stands for A or G; Y for T or C, '/' indicates a cleavage position). Here, we report the crystal structures of the Bse634I R226A mutant complexed with cognate oligoduplexes containing ACCGGT and GCCGGC sites, respectiv...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks300
更新日期:2012-08-01 00:00:00
abstract::MiR-210 is up-regulated in multiple cancer types but its function is disputable and further investigation is necessary. Using a bioinformatics approach, we identified the putative target genes of miR-210 in hypoxia-induced CNE cells from genome-wide scale. Two functional gene groups related to cell cycle and RNA proce...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks995
更新日期:2013-01-07 00:00:00
abstract::Immunoglobulin genes contain a conserved eight base sequence element 5' to the site of transcription initiation. This octamer can serve as a site for the binding of nuclear proteins which are presumably involved in the cell type specific expression of this family of genes. In studying the binding of nuclear proteins t...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/16.12.5503
更新日期:1988-06-24 00:00:00
abstract::Gene expression in Plasmodium falciparum is tightly regulated to ensure successful propagation of the parasite throughout its complex life cycle. The earliest transcriptomics studies in P. falciparum suggested a cascade of transcriptional activity over the course of the 48-hour intraerythrocytic developmental cycle (I...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx464
更新日期:2017-07-27 00:00:00
abstract::We recently reported that the antitumor triazoloacridone, compound C-1305, is a topoisomerase II poison with unusual properties. In this study we characterize the DNA interactions of C-1305 in vitro, in comparison with other topoisomerase II inhibitors. Our results show that C-1305 binds to DNA by intercalation and po...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gki904
更新日期:2005-10-27 00:00:00
abstract::The National Center for Biotechnology Information (NCBI) provides a large suite of online resources for biological information and data, including the GenBank® nucleic acid sequence database and the PubMed® database of citations and abstracts published in life science journals. The Entrez system provides search and re...
journal_title:Nucleic acids research
pub_type: 杂志文章,评审
doi:10.1093/nar/gkaa892
更新日期:2021-01-08 00:00:00
abstract::The tumor suppressor p53 is a sequence-specific transcription factor, which regulates the expression of target genes involved in different stress responses. To understand p53's essential transcriptional functions, unbiased analysis of its DNA-binding repertoire is pivotal. In a genome-wide tiling ChIP-on-chip approach...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn232
更新日期:2008-06-01 00:00:00