RESUMO
In all domains of life, RNA chaperones safeguard and guide the fate of the cellular RNA pool. RNA chaperones comprise structurally diverse proteins that ensure proper folding, stability, and ribonuclease resistance of RNA, and they support regulatory activities mediated by RNA. RNA chaperones constitute a topologically diverse group of proteins that often present an unstructured region and bind RNA with limited nucleotide sequence preferences. In bacteria, three main proteins - Hfq, ProQ, and CsrA - have been shown to regulate numerous complex processes, including bacterial growth, stress response and virulence. Hfq and ProQ have well-studied activities as global chaperones with pleiotropic impact, while CsrA has a chaperone-like role with more defined riboregulatory function. Here, we describe relevant novel insights into their common features, including RNA binding properties, unstructured domains, and interplay with other proteins important to RNA metabolism.
Assuntos
RNA Bacteriano , Pequeno RNA não Traduzido , Bactérias/genética , Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Fator Proteico 1 do Hospedeiro/genética , Fator Proteico 1 do Hospedeiro/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , RNA Bacteriano/metabolismo , Pequeno RNA não Traduzido/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
In organisms from all domains of life, multi-enzyme assemblies play central roles in defining transcript lifetimes and facilitating RNA-mediated regulation of gene expression. An assembly dedicated to such roles, known as the RNA degradosome, is found amongst bacteria from highly diverse lineages. About a fifth of the assembly mass of the degradosome of Escherichia coli and related species is predicted to be intrinsically disordered - a property that has been sustained for over a billion years of bacterial molecular history and stands in marked contrast to the high degree of sequence variation of that same region. Here, we characterize the conformational dynamics of the degradosome using a hybrid structural biology approach that combines solution scattering with ad hoc ensemble modelling, cryo-electron microscopy, and other biophysical methods. The E. coli degradosome can form punctate bodies in vivo that may facilitate its functional activities, and based on our results, we propose an electrostatic switch model to account for the propensity of the degradosome to undergo programmable puncta formation.
Assuntos
Endorribonucleases , Proteínas de Escherichia coli/metabolismo , Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Complexos Multienzimáticos , Polirribonucleotídeo Nucleotidiltransferase , RNA Helicases , RNA Bacteriano/metabolismo , Domínio Catalítico , Microscopia Crioeletrônica , Ensaio de Desvio de Mobilidade Eletroforética , Endorribonucleases/genética , Endorribonucleases/metabolismo , Escherichia coli/metabolismo , Escherichia coli/ultraestrutura , Proteínas de Escherichia coli/genética , Proteínas Intrinsicamente Desordenadas/genética , Proteínas Intrinsicamente Desordenadas/metabolismo , Modelos Estruturais , Mutação , Processamento Pós-Transcricional do RNA , RNA Bacteriano/genética , Ribonucleases/genética , Ribonucleases/metabolismo , Eletricidade Estática , TomografiaRESUMO
BACKGROUND: Psychomotor agitation is a common condition in patients with psychotic disorders. One treatment possibility is intramuscular (IM) second-generation antipsychotics. Yet their efficacy in this formulation and for this aim is unclear. This network meta-analysis aims to evaluate the efficacy of short-acting IM second-generation antipsychotic drugs, haloperidol and placebo in patients with diagnosis of schizophrenia and schizophrenia-like disorders that present acute agitation. METHODS: We searched the Cochrane Schizophrenia Group Controlled Trials Register, MEDLINE, EMBASE, PsycINFO, Cochrane Library, PubMed, BIOSIS, ClinicalTrials.gov and WHO ICTRP up to November 2018 and PubMed until March 2020. Study selection and outcome extraction were performed independently by two reviewers. Pairwise and network meta-analyses were conducted to compare the different IM second-generation antipsychotics among themselves and with IM haloperidol and placebo. The primary outcome was the number of responders at 2 h after the first injection. Responders at 24 h were also analysed. RESULTS: 10 studies with 1964 patients were included in the meta-analysis. Ziprasidone, olanzapine, aripiprazole and haloperidol were more efficacious than placebo in calming patients at 2 h after administration. Furthermore, olanzapine was superior to aripiprazole. The results at 24 h confirmed the superiority of aripiprazole, olanzapine and haloperidol over placebo, while for ziprasidone no data were available. CONCLUSIONS: All second-generation antipsychotics available as intramuscular medications were effective in reducing agitation in people with schizophrenia. Olanzapine was somewhat more efficacious than aripiprazole.
