Base de dados : MEDLINE
Pesquisa : D08.811.797 [Categoria DeCS]
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[PMID]:29339152
[Au] Autor:Gulshan MA; Rahman MM; Matsumura S; Higuchi T; Umezawa N; Ikawa Y
[Ad] Endereço:Department of Chemistry, Graduate School of Science and Engineering, University of Toyama, Gofuku 3190, Toyama, 930-8555, Japan; Graduate School of Innovative Life Science, University of Toyama, Gofuku 3190, Toyama, 930-8555, Japan.
[Ti] Título:Biogenic triamine and tetraamine activate core catalytic ability of Tetrahymena group I ribozyme in the absence of its large activator module.
[So] Source:Biochem Biophys Res Commun;496(2):594-600, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Group I intron ribozymes share common core elements that form a three-dimensional structure responsible for their catalytic activity. This core structure is unstable without assistance from additional factors that stabilize its tertiary structure. We examined biogenic triamine and tetraamine and also their fragments for their abilities to stabilize a structurally unstable group I ribozyme, ΔP5 ribozyme, derived from the Tetrahymena group I intron ribozyme by deleting its large activator module. Biogenic triamine (spermidine) and tetraamine (spermine) efficiently activated the ΔP5 ribozyme under conditions where the ribozyme was virtually inactive. These observations suggested that polyamines are promising small molecule modulators to activate and possibly inhibit the core catalytic ability of group I ribozymes.
[Mh] Termos MeSH primário: Poliaminas/metabolismo
RNA Catalítico/metabolismo
Tetrahymena/enzimologia
[Mh] Termos MeSH secundário: Sequência de Bases
Domínio Catalítico
Cinética
Magnésio/metabolismo
Conformação de Ácido Nucleico
RNA Catalítico/química
Espermidina/metabolismo
Tetrahymena/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (GIR1 ribozyme); 0 (Polyamines); 0 (RNA, Catalytic); I38ZP9992A (Magnesium); U87FK77H25 (Spermidine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE


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[PMID]:28454775
[Au] Autor:Eggert F; Kulikov K; Domnick C; Leifels P; Kath-Schorr S
[Ad] Endereço:LIMES Institute, Chemical Biology & Medicinal Chemistry Unit, University of Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn, Germany.
[Ti] Título:Iluminated by foreign letters - Strategies for site-specific cyclopropene modification of large functional RNAs via in vitro transcription.
[So] Source:Methods;120:17-27, 2017 May 01.
[Is] ISSN:1095-9130
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The synthesis of sequence-specifically modified long RNA molecules, which cannot entirely be prepared via solid phase synthesis methods is experimentally challenging. We are using a new approach based on an expanded genetic alphabet preparing site-specifically modified RNA molecules via standard in vitro transcription. In this report, the site-specific labeling of functional RNAs, in particular ribozymes and a long non-coding RNA with cyclopropene moieties, is presented. We provide detailed instructions for RNA labeling via in vitro transcription and include required analytical methods to verify production and identity of the transcript. We further present post-transcriptional inverse electron demand Diels-Alder cycloaddition reactions on the cyclopropene-modified sequences and discuss applications of the genetic alphabet expansion transcription for in vitro preparation of labeled functional RNAs with complex foldings. In detail, the glmS and CPEB3 ribozymes were site-specifically decorated with methyl cyclopropene moieties using the unnatural TPT3 triphosphate and were proven to be still functional. In addition, the structurally complex A region of the Xist lncRNA (401nt) was site-specifically modified with methyl cyclopropene and detected by fluorescence after cycloaddition reaction with a tetrazine-BODIPY conjugate.
[Mh] Termos MeSH primário: Reação de Cicloadição/métodos
Ciclopropanos/química
RNA Catalítico/química
RNA Longo não Codificante/química
Coloração e Rotulagem/métodos
[Mh] Termos MeSH secundário: Elétrons
Corantes Fluorescentes/química
Técnicas In Vitro/métodos
Nucleotídeos/química
Processamento Pós-Transcricional do RNA
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclopropanes); 0 (Fluorescent Dyes); 0 (Nucleotides); 0 (RNA, Catalytic); 0 (RNA, Long Noncoding); J6UJO23JGU (1-methylcyclopropene)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


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[PMID]:29059242
[Au] Autor:Sun X; Chen W; He L; Sheng J; Liu Y; Vu GP; Yang Z; Li W; Trang P; Wang Y; Hai R; Zhu H; Lu S; Liu F
[Ad] Endereço:College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, China.
[Ti] Título:Inhibition of human cytomegalovirus immediate early gene expression and growth by a novel RNase P ribozyme variant.
[So] Source:PLoS One;12(10):e0186791, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We have previously engineered new RNase P-based ribozyme variants with improved in vitro catalytic activity. In this study, we employed a novel engineered variant to target a shared mRNA region of human cytomegalovirus (HCMV) immediate early proteins 1 (IE1) and 2 (IE2), which are essential for the expression of viral early and late genes as well as viral growth. Ribozyme F-R228-IE represents a novel variant that possesses three unique base substitution point mutations at the catalytic domain of RNase P catalytic RNA. Compared to F-M1-IE that is the ribozyme derived from the wild type RNase P catalytic RNA sequence, the functional variant F-R228-IE cleaved the target mRNA sequence in vitro at least 100 times more efficiently. In cultured cells, expression of F-R228-IE resulted in IE1/IE2 expression reduction by 98-99% and in HCMV production reduction by 50,000 folds. In contrast, expression of F-M1-IE resulted in IE1/IE2 expression reduction by less than 80% and in viral production reduction by 200 folds. Studies of the ribozyme-mediated antiviral effects in cultured cells suggest that overall viral early and late gene expression and viral growth were inhibited due to the ribozyme-mediated reduction of HCMV IE1 and IE2 expression. Our results provide direct evidence that engineered RNase P ribozymes, such as F-R228-IE, can serve as a novel class of inhibitors for the treatment and prevention of HCMV infection. Moreover, these results suggest that F-R228-IE, with novel and unique mutations at the catalytic domain to enhance ribozyme activity, can be a candidate for the construction of effective agents for anti-HCMV therapy.
[Mh] Termos MeSH primário: Citomegalovirus/genética
Genes Precoces
RNA Catalítico/metabolismo
Ribonuclease P/metabolismo
[Mh] Termos MeSH secundário: Citomegalovirus/crescimento & desenvolvimento
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Catalytic); EC 3.1.26.5 (Ribonuclease P)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171024
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186791


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[PMID]:28951565
[Au] Autor:Shi Y
[Ad] Endereço:Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
[Ti] Título:Mechanistic insights into precursor messenger RNA splicing by the spliceosome.
[So] Source:Nat Rev Mol Cell Biol;18(11):655-670, 2017 Nov.
[Is] ISSN:1471-0080
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Precursor messenger RNA (pre-mRNA) splicing is an essential step in the flow of information from DNA to protein in all eukaryotes. Research over the past four decades has molecularly delineated the splicing pathway, including characterization of the detailed splicing reaction, definition of the spliceosome and identification of its components, and biochemical analysis of the various splicing complexes and their regulation. Structural information is central to mechanistic understanding of pre-mRNA splicing by the spliceosome. X-ray crystallography of the spliceosomal components and subcomplexes is complemented by electron microscopy of the intact spliceosome. In this Review, I discuss recent atomic-resolution structures of the intact spliceosome at different stages of the splicing cycle. These structures have provided considerable mechanistic insight into pre-mRNA splicing and have corroborated and explained a large body of genetic and biochemical data. Together, the structural data have proved that the spliceosome is a protein-directed metalloribozyme.
[Mh] Termos MeSH primário: Precursores de RNA/química
Processamento de RNA/fisiologia
RNA Catalítico/química
Spliceossomos/ultraestrutura
[Mh] Termos MeSH secundário: Animais
Cristalografia por Raios X
Seres Humanos
Microscopia Eletrônica
Precursores de RNA/genética
Precursores de RNA/metabolismo
RNA Catalítico/genética
RNA Catalítico/metabolismo
Spliceossomos/genética
Spliceossomos/metabolismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (RNA Precursors); 0 (RNA, Catalytic)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170928
[St] Status:MEDLINE
[do] DOI:10.1038/nrm.2017.86


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[PMID]:28934478
[Au] Autor:Daher M; Mustoe AM; Morriss-Andrews A; Brooks Iii CL; Walter NG
[Ad] Endereço:Single Molecule Analysis Group and Center for RNA Biomedicine, Department of Chemistry, University of Michigan, 930 N. University Avenue, Ann Arbor, MI 48109-1055, USA.
[Ti] Título:Tuning RNA folding and function through rational design of junction topology.
[So] Source:Nucleic Acids Res;45(16):9706-9715, 2017 Sep 19.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Structured RNAs such as ribozymes must fold into specific 3D structures to carry out their biological functions. While it is well-known that architectural features such as flexible junctions between helices help guide RNA tertiary folding, the mechanisms through which junctions influence folding remain poorly understood. We combine computational modeling with single molecule Förster resonance energy transfer (smFRET) and catalytic activity measurements to investigate the influence of junction design on the folding and function of the hairpin ribozyme. Coarse-grained simulations of a wide range of junction topologies indicate that differences in sterics and connectivity, independent of stacking, significantly affect tertiary folding and appear to largely explain previously observed variations in hairpin ribozyme stability. We further use our simulations to identify stabilizing modifications of non-optimal junction topologies, and experimentally validate that a three-way junction variant of the hairpin ribozyme can be stabilized by specific insertion of a short single-stranded linker. Combined, our multi-disciplinary study further reinforces that junction sterics and connectivity are important determinants of RNA folding, and demonstrates the potential of coarse-grained simulations as a tool for rationally tuning and optimizing RNA folding and function.
[Mh] Termos MeSH primário: Dobramento de RNA
RNA Catalítico/química
[Mh] Termos MeSH secundário: Transferência Ressonante de Energia de Fluorescência
Modelos Moleculares
RNA Catalítico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Catalytic); 0 (hairpin ribozyme)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx614


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[PMID]:28825710
[Au] Autor:Panja S; Hua B; Zegarra D; Ha T; Woodson SA
[Ad] Endereço:T.C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, Maryland, USA.
[Ti] Título:Metals induce transient folding and activation of the twister ribozyme.
[So] Source:Nat Chem Biol;13(10):1109-1114, 2017 Oct.
[Is] ISSN:1552-4469
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Twister is a small ribozyme present in almost all kingdoms of life that rapidly self-cleaves in variety of divalent metal ions. We used activity assays, bulk FRET and single-molecule FRET (smFRET) to understand how different metal ions promote folding and self-cleavage of the Oryza sativa twister ribozyme. Although most ribozymes require additional Mg for catalysis, twister inverts this expectation, requiring 20-30 times less Mg to self-cleave than to fold. Transition metals such as Co , Ni and Zn activate twister more efficiently than Mg ions. Although twister is fully active in ≤ 0.5 mM MgCl , smFRET experiments showed that the ribozyme visits the folded state infrequently under these conditions. Comparison of folding and self-cleavage rates indicates that most folding events lead to catalysis, which correlates with metal bond strength. Thus, the robust activity of twister reports on transient metal ion binding under physiological conditions.
[Mh] Termos MeSH primário: Magnésio/farmacologia
Conformação de Ácido Nucleico/efeitos dos fármacos
Oryza/enzimologia
RNA Catalítico/química
RNA Catalítico/metabolismo
Zinco/farmacologia
[Mh] Termos MeSH secundário: Ativação Enzimática/efeitos dos fármacos
Transferência Ressonante de Energia de Fluorescência
Magnésio/química
Oryza/genética
Zinco/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Catalytic); I38ZP9992A (Magnesium); J41CSQ7QDS (Zinc)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170822
[St] Status:MEDLINE
[do] DOI:10.1038/nchembio.2459


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[PMID]:28814522
[Au] Autor:Liu ZY; Yu JY; Huang XY; Fan H; Li XF; Deng YQ; Ji X; Cheng ML; Ye Q; Zhao H; Han JF; An XP; Jiang T; Zhang B; Tong YG; Qin CF
[Ad] Endereço:State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
[Ti] Título:Characterization of -Acting RNA Elements of Zika Virus by Using a Self-Splicing Ribozyme-Dependent Infectious Clone.
[So] Source:J Virol;91(21), 2017 Nov 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Zika virus (ZIKV) has caused significant outbreaks and epidemics in the Americas recently, raising global concern due to its ability to cause microcephaly and other neurological complications. A stable and efficient infectious clone of ZIKV is urgently needed. However, the instability and toxicity of flavivirus cDNA clones in hosts has hindered the development of ZIKV infectious clones. Here, using a novel self-splicing ribozyme-based strategy, we generated a stable infectious cDNA clone of a contemporary ZIKV strain imported from Venezuela to China in 2016. The constructed clone contained a modified version of the group II self-splicing intron near the junction between the E and NS1 genes, which were removed from the RNA transcripts by an easy-to-establish splicing reaction. Transfection of the spliced RNAs into BHK-21 cells led to the production of infectious progeny virus that resembled the parental virus. Finally, potential -acting RNA elements in ZIKV genomic RNA were identified based on this novel reverse genetics system, and the critical role of 5'-SLA promoter and 5'-3' cyclization sequences were characterized by a combination of different assays. Our results provide another stable and reliable reverse genetics system for ZIKV that will help study ZIKV infection and pathogenesis, and the novel self-splicing intron-based strategy could be further expanded for the construction of infectious clones from other emerging and reemerging flaviviruses. The ongoing Zika virus (ZIKV) outbreaks have drawn global concern due to the unexpected causal link to fetus microcephaly and other severe neurological complications. The infectious cDNA clones of ZIKV are critical for the research community to study the virus, understand the disease, and inform vaccine design and antiviral screening. A panel of existing technologies have been utilized to develop ZIKV infectious clones. Here, we successfully generated a stable infectious clone of a 2016 ZIKV strain using a novel self-splicing ribozyme-based technology that abolished the potential toxicity of ZIKV cDNA clones to the host. Moreover, two crucial -acting replication elements (5'-SLA and 5'-CS) of ZIKV were first identified using this novel reverse genetics system. This novel self-splicing ribozyme-based reverse genetics platform will be widely utilized in future ZIKV studies and provide insight for the development of infectious clones of other emerging viruses.
[Mh] Termos MeSH primário: Processamento de RNA
RNA Catalítico/metabolismo
Sequências Reguladoras de Ácido Ribonucleico/genética
Infecção pelo Zika virus/virologia
Zika virus/genética
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Clonagem Molecular
Cricetinae
DNA Complementar
Regulação Viral da Expressão Gênica
Rim/metabolismo
Rim/virologia
Camundongos Endogâmicos BALB C
RNA Catalítico/genética
Genética Reversa
Carga Viral
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Complementary); 0 (RNA, Catalytic); 0 (Regulatory Sequences, Ribonucleic Acid)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170818
[St] Status:MEDLINE


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[PMID]:28787138
[Au] Autor:Bingaman JL; Gonzalez IY; Wang B; Bevilacqua PC
[Ad] Endereço:Department of Chemistry, Pennsylvania State University , University Park, Pennsylvania 16802, United States.
[Ti] Título:Activation of the glmS Ribozyme Nucleophile via Overdetermined Hydrogen Bonding.
[So] Source:Biochemistry;56(33):4313-4317, 2017 Aug 22.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RNA enzymes, or ribozymes, catalyze internal phosphodiester bond cleavage using diverse catalytic strategies. These include the four classic strategies: in-line nucleophilic attack, deprotonation of the 2'-OH nucleophile, protonation of the 5'-O leaving group, and stabilization of developing charge on the nonbridging oxygen atoms of the scissile phosphate. In addition, we recently identified two additional ribozyme strategies: acidification of the 2'-OH and release of the 2'-OH from inhibitory interactions. Herein, we report inverse thio effects in the presence of glmS ribozyme variants and a 1-deoxyglucosamine 6-phosphate cofactor analogue and demonstrate that activation of the 2'-OH nucleophile is promoted by competitive hydrogen bonding among diverse ribozyme moieties for the pro-R nonbridging oxygen. We conclude that the glmS ribozyme uses an overdetermined set of competing hydrogen bond donors in its active site to ensure potent activation and regulation by the cofactor. Nucleophile activation through competitive, overdetermined hydrogen bonding could be a general strategy for ribozyme activation and may be applicable for controlling the function of ribozymes and riboswitches in the laboratory.
[Mh] Termos MeSH primário: Conformação de Ácido Nucleico
RNA Bacteriano/química
RNA Catalítico/química
[Mh] Termos MeSH secundário: Ligações de Hidrogênio
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Bacterial); 0 (RNA, Catalytic)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170831
[Lr] Data última revisão:
170831
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170809
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00662


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[PMID]:28786485
[Au] Autor:Agmon I
[Ad] Endereço:Institute for Advanced Studies in Theoretical Chemistry, Schulich Faculty of Chemistry, Technion - Israel Institute of Technology, Haifa, Israel.
[Ti] Título:Sequence complementarity at the ribosomal Peptidyl Transferase Centre implies self-replicating origin.
[So] Source:FEBS Lett;591(20):3252-3258, 2017 Oct.
[Is] ISSN:1873-3468
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A feasible scenario for the emergence of life requires the spontaneous materialization and sustainability of a proto-ribosome that could have catalysed the formation of the first peptides. Models of proto-ribosomes were derived from the ribosomal Peptidyl Transferase Centre (PTC) region, but the poor prebiotic copying abilities give rise to the question of their mode of replication. Here, complementarity is demonstrated in bacterial ribosomes, between nucleotides that constitute the two halves of the PTC cavity. The complementarity corroborates the dimeric nature of the proto-ribosome and is likely to underlie the symmetry of the PTC region. Furthermore, it indicates a simple and efficient replication mode; the strand of each monomer could have acted as a template for the synthesis of its counterpart, forming a self-replicating ribozyme.
[Mh] Termos MeSH primário: Origem da Vida
Peptidil Transferases/química
RNA Catalítico/química
RNA Ribossômico 23S/química
Ribossomos/metabolismo
[Mh] Termos MeSH secundário: Pareamento de Bases
Biocatálise
Escherichia coli/genética
Escherichia coli/metabolismo
Evolução Molecular
Modelos Biológicos
Modelos Moleculares
Conformação de Ácido Nucleico
Peptidil Transferases/genética
Peptidil Transferases/metabolismo
RNA Catalítico/genética
RNA Catalítico/metabolismo
RNA Ribossômico 23S/genética
RNA Ribossômico 23S/metabolismo
Ribossomos/genética
Ribossomos/ultraestrutura
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Catalytic); 0 (RNA, Ribosomal, 23S); EC 2.3.2.12 (Peptidyl Transferases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170809
[St] Status:MEDLINE
[do] DOI:10.1002/1873-3468.12781


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[PMID]:28715844
[Au] Autor:Froebel BR; Trujillo AJ; Sullivan JM
[Ad] Endereço:Research Service, VA Western New York Healthcare System, Buffalo, New York, United States 2Department of Ophthalmology, State University of New York, University at Buffalo, Buffalo, New York, United States 3The Ross Eye Institute of University at Buffalo, Buffalo, New York, United States.
[Ti] Título:Effects of Pathogenic Variations in the Human Rhodopsin Gene (hRHO) on the Predicted Accessibility for a Lead Candidate Ribozyme.
[So] Source:Invest Ophthalmol Vis Sci;58(9):3576-3591, 2017 Jul 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: The mutation-independent strategy for hammerhead ribozyme (hhRz) or RNA interference (RNAi)-based gene therapeutics to treat autosomal dominant diseases is predicated on the hypothesis that a single therapeutic would equivalently suppress all/most of the diverse mutant mRNAs in patients with the disease phenotype. However, the hypothesis has not been formally tested. We address this through a comprehensive bioinformatics study of how mutations affect target mRNA structure accessibility for a single lead hhRz therapeutic (725GUC↓), designed against human rod rhodopsin mRNA (hRHO), for patients with hRHO mutations that cause autosomal dominant retinitis pigmentosa. Methods: A total of 199 in silico coding region mutations (missense, nonsense, insert, deletion, indel) were made in hRHO mRNA based on Human Gene Mutation Database and Database of Single Nucleotide Polymorphisms. Each mRNA was folded with MFold, SFold, and OligoWalk algorithms and subjected to a bioinformatics model called multiparameter prediction of RNA accessibility. Predicted accessibility of each mutant over both a broad local region and the explicit lead ribozyme annealing site were compared quantitatively to wild-type hRHO mRNA. Results: Accessibility of the 725GUC↓ site is sensitive to some mutations. For single nucleotide missense mutations, proximity of the mutation to the hhRz annealing site increases the impact on predicted accessibility, but some distant mutations also influence accessibility. Conclusions: A mutation-independent strategy appears viable in this specific context but certain mutations could significantly influence ribozyme or RNAi efficacy through impact on accessibility at the target annealing site/region. This possibility must be considered in applications of this gene therapy strategy.
[Mh] Termos MeSH primário: Códon sem Sentido/genética
Mutação de Sentido Incorreto/genética
Polimorfismo de Nucleotídeo Único
RNA Catalítico/genética
RNA Mensageiro/genética
Retinite Pigmentosa/genética
Rodopsina/genética
[Mh] Termos MeSH secundário: Biologia Computacional
Análise Mutacional de DNA
Seres Humanos
Interferência de RNA
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Codon, Nonsense); 0 (RNA, Catalytic); 0 (RNA, Messenger); 0 (hammerhead ribozyme); 9009-81-8 (Rhodopsin)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170728
[Lr] Data última revisão:
170728
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170718
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.16-20877



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BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde