Sequence-specific cleavage of the RNA strand in DNA–RNA hybrids by the fusion of ribonuclease H with a zinc finger

Sulej, Agata; Tuszyńska, Irina; Skowronek, Krzysztof; Nowotny, Marcin; Bujnicki, Janusz M.

doi:10.1093/nar/gks885

Cited by 23 publications

(19 citation statements)

References 35 publications

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“…Transposases of TEs, as well as the mammalian recombination-activating gene 1 (RAG1) enzyme, also contain ZNF domains that govern dsDNA binding ( Yurchenko et al, 2003 ). ZNF domains with desired sequence specificities can be artificially fused to an RNase H enzyme to achieve cleavage at specific target DNA sequences with potential use in gene therapy ( Sulej et al, 2012 ). Transposases, the most abundant RNase H-like proteins ( Majorek et al, 2014 ), mediate cut-and-paste of DNA transposons, a phenomenon originally described by McClintock (1951) .…”

Section: Rnase H Family Membersmentioning

confidence: 99%

RNase H As Gene Modifier, Driver of Evolution and Antiviral Defense

et al. 2017

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Retroviral infections are ‘mini-symbiotic’ events supplying recipient cells with sequences for viral replication, including the reverse transcriptase (RT) and ribonuclease H (RNase H). These proteins and other viral or cellular sequences can provide novel cellular functions including immune defense mechanisms. Their high error rate renders RT-RNases H drivers of evolutionary innovation. Integrated retroviruses and the related transposable elements (TEs) have existed for at least 150 million years, constitute up to 80% of eukaryotic genomes and are also present in prokaryotes. Endogenous retroviruses regulate host genes, have provided novel genes including the syncytins that mediate maternal-fetal immune tolerance and can be experimentally rendered infectious again. The RT and the RNase H are among the most ancient and abundant protein folds. RNases H may have evolved from ribozymes, related to viroids, early in the RNA world, forming ribosomes, RNA replicases and polymerases. Basic RNA-binding peptides enhance ribozyme catalysis. RT and ribozymes or RNases H are present today in bacterial group II introns, the precedents of TEs. Thousands of unique RTs and RNases H are present in eukaryotes, bacteria, and viruses. These enzymes mediate viral and cellular replication and antiviral defense in eukaryotes and prokaryotes, splicing, R-loop resolvation, DNA repair. RNase H-like activities are also required for the activity of small regulatory RNAs. The retroviral replication components share striking similarities with the RNA-induced silencing complex (RISC), the prokaryotic CRISPR-Cas machinery, eukaryotic V(D)J recombination and interferon systems. Viruses supply antiviral defense tools to cellular organisms. TEs are the evolutionary origin of siRNA and miRNA genes that, through RISC, counteract detrimental activities of TEs and chromosomal instability. Moreover, piRNAs, implicated in transgenerational inheritance, suppress TEs in germ cells. Thus, virtually all known immune defense mechanisms against viruses, phages, TEs, and extracellular pathogens require RNase H-like enzymes. Analogous to the prokaryotic CRISPR-Cas anti-phage defense possibly originating from TEs termed casposons, endogenized retroviruses ERVs and amplified TEs can be regarded as related forms of inheritable immunity in eukaryotes. This survey suggests that RNase H-like activities of retroviruses, TEs, and phages, have built up innate and adaptive immune systems throughout all domains of life.

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Section: Rnase H Family Membersmentioning

confidence: 99%

RNase H As Gene Modifier, Driver of Evolution and Antiviral Defense

et al. 2017

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“…The NPDock server is designed to automate the procedure of protein–nucleic acid complex structure modeling. Published examples of structural models developed with the computational pipeline corresponding to NPDock include Trm14 methyltransferase complexed with tRNA ( 28 ), and an engineered RNaseH-zinc finger fusion protein complexed to an RNA–DNA hybrid ( 29 ). The server was launched in December 2013 as RNPdock and had the capability to dock protein–RNA complexes with the use of the DARS-RNP and QUASI-RNP potentials ( 15 ).…”

Section: Resultsmentioning

confidence: 99%

NPDock: a web server for protein–nucleic acid docking

et al. 2015

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Protein–RNA and protein–DNA interactions play fundamental roles in many biological processes. A detailed understanding of these interactions requires knowledge about protein–nucleic acid complex structures. Because the experimental determination of these complexes is time-consuming and perhaps futile in some instances, we have focused on computational docking methods starting from the separate structures. Docking methods are widely employed to study protein–protein interactions; however, only a few methods have been made available to model protein–nucleic acid complexes. Here, we describe NPDock (Nucleic acid–Protein Docking); a novel web server for predicting complexes of protein–nucleic acid structures which implements a computational workflow that includes docking, scoring of poses, clustering of the best-scored models and refinement of the most promising solutions. The NPDock server provides a user-friendly interface and 3D visualization of the results. The smallest set of input data consists of a protein structure and a DNA or RNA structure in PDB format. Advanced options are available to control specific details of the docking process and obtain intermediate results. The web server is available at http://genesilico.pl/NPDock.

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“…International Institute of Molecular and Cell Biology in Warsaw (IIMCB) hosts a group of one of the authors of this article (Janusz Bujnicki), which is working on a variety of topics, including the development of predictive methods and their application in, e.g., protein structure prediction [57], prediction of intrinsic disorder in proteins [58], and prediction of protein-RNA interactions [59]. They are also involved in comparative bioinformatics of protein superfamilies [60] and in experimental protein engineering guided by bioinformatics [61]. Another area of their research is the development of databases of information about pathways of nucleic acid metabolism [62].…”

Section: Main Bioinformatics Research Centers In Polandmentioning

confidence: 99%