RESUMO
RNA silencing negatively regulates gene expression at transcriptional and posttranscriptional levels, guided by small RNA molecules. It modulates core regulatory pathways across the eukaryotes, such as developmental processes or stress responses. The widespread existence of this phenomenon and the key pathways regulated have led to the development of a new technology based on the modification of gene expression, which has been applied successfully in different areas such as medicine or agriculture. Here we review the most important patents related to RNA silencing across the life kingdoms, including biotechnological applications into medicine, crop science and bioengineering.
Assuntos
Engenharia Biomédica/métodos , Terapia Genética/métodos , Oligonucleotídeos Antissenso/farmacologia , Interferência de RNA/efeitos dos fármacos , RNA Interferente Pequeno/farmacologia , Fungos/efeitos dos fármacos , Fungos/genética , Fungos/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Infecções por Herpesviridae/tratamento farmacológico , Infecções por Herpesviridae/patologia , Infecções por Herpesviridae/virologia , Herpesvirus Humano 8/efeitos dos fármacos , Herpesvirus Humano 8/crescimento & desenvolvimento , Humanos , MicroRNAs/genética , Oligonucleotídeos Antissenso/uso terapêutico , Vírus da Parainfluenza 1 Humana/efeitos dos fármacos , Vírus da Parainfluenza 1 Humana/crescimento & desenvolvimento , Infecções por Paramyxoviridae/tratamento farmacológico , Infecções por Paramyxoviridae/patologia , Infecções por Paramyxoviridae/virologia , Patentes como Assunto , Plantas/efeitos dos fármacos , Plantas/genética , Plantas/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , RNA Interferente Pequeno/uso terapêutico , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/patologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Vírus Sinciciais Respiratórios/crescimento & desenvolvimentoRESUMO
Fur (ferric uptake regulator) proteins are principally responsible for maintaining iron homeostasis in prokaryotes. Iron is usually a scarce resource. Its limitation reduces photosynthetic rates and cell growth in cyanobacteria in general and especially in cyanobacteria that are fixing dinitrogen, a process that requires the synthesis of numerous proteins with a high content of iron. This paper shows that in the diazotrophic cyanobacterium Anabaena sp. strain PCC 7120, levels of furA mRNA and FurA protein increase significantly in response to nitrogen deprivation, and that furA up-regulation takes place specifically in proheterocysts and mature heterocysts. Great differences in a Northern blot, probed with furA, of RNA from an ntcA mutant relative to wild-type Anabaena sp. were attributable to binding of NtcA, a global regulator of nitrogen metabolism, to the promoter of furA and to the promoter of the furA antisense transcript alr1690-alpha-furA.
Assuntos
Anabaena/genética , Anabaena/metabolismo , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Proteínas Repressoras/genética , Fatores de Transcrição/metabolismo , Anabaena/crescimento & desenvolvimento , Proteínas de Bactérias/genética , Sequência de Bases , Ferro/metabolismo , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Ligação Proteica , RNA Antissenso/metabolismo , RNA Bacteriano/metabolismo , RNA Mensageiro/metabolismo , Proteínas Repressoras/metabolismoRESUMO
The Fur (ferric uptake regulator) protein is a global regulator in most prokaryotes that controls a large number of genes. Fur is a classical repressor that uses ferrous iron as co-repressor and binds to specific DNA sequences (iron boxes) as a dimer. Three different genes coding for Fur homologues have been identified in Anabaena sp. PCC 7120. FurA controls the transcription of flavodoxin, the product of the isiB gene, and is moderately autoregulated. In this work, the promoter of the furA gene was defined and the FurA protected regions in the furA and isiB promoters were identified, showing that the binding sites for Anabaena FurA contain A/T-rich sequences with a variable arrangement compared to the conventional 19-base pair Fur consensus. The influence of different factors on the interaction between FurA and the promoters was evaluated in vitro. The affinity of FurA for the DNA targets was significantly affected by the redox status of this regulator and the presence of Mn(2+). The optimal binding conditions were observed in the presence of both Mn(2+) and DTT. Those results suggest that, in addition to iron availability, FurA-DNA interaction is modulated by redox conditions.
