RESUMEN
MicroRNAs (miRNAs) play crucial regulatory roles in controlling immune responses, but their dynamic expression mechanisms are poorly understood. Here, we firstly confirm that the conserved miRNA miR-210 negatively regulates innate immune responses of Drosophila and human via targeting Toll and TLR6, respectively. Secondly, our findings demonstrate that the expression of miR-210 is dynamically regulated by NF-κB factor Dorsal in immune response of Drosophila Toll pathway. Thirdly, we find that Dorsal-mediated transcriptional inhibition of miR-210 is dependent on the transcriptional repressor Su(Hw). Mechanistically, Dorsal interacts with Su(Hw) to modulate cooperatively the dynamic expression of miR-210 in a time- and dose-dependent manner, thereby controlling the strength of Drosophila Toll immune response and maintaining immune homeostasis. Fourthly, we reveal a similar mechanism in human cells, where NF-κB/RelA cooperates with E4F1 to regulate the dynamic expression of hsa-miR-210 in the TLR immune response. Overall, our study reveals a conservative regulatory mechanism that maintains animal innate immune homeostasis and provides new insights into the dynamic regulation of miRNA expression in immune response.
RESUMEN
Drosophila Myc (dMyc), as a broad-spectrum transcription factor, can regulate the expression of a large number of genes to control diverse cellular processes, such as cell cycle progression, cell growth, proliferation and apoptosis. However, it remains largely unknown about whether dMyc can be involved in Drosophila innate immune response. Here, we have identified dMyc to be a negative regulator of Drosophila Imd pathway via the loss- and gain-of-function screening. We demonstrate that dMyc inhibits Drosophila Imd immune response via directly activating miR-277 transcription, which further inhibit the expression of imd and Tab2-Ra/b. Importantly, dMyc can improve the survival of flies upon infection, suggesting inhibiting Drosophila Imd pathway by dMyc is vital to restore immune homeostasis that is essential for survival. Taken together, our study not only reports a new dMyc-miR-277-imd/Tab2 axis involved in the negative regulation of Drosophila Imd pathway, and provides a new insight into the complex regulatory mechanism of Drosophila innate immune homeostasis maintenance.
Asunto(s)
Proteínas de Unión al ADN/genética , Proteínas de Drosophila/genética , Inmunidad Innata/genética , MicroARNs/genética , Factores de Transcripción/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , División Celular/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Regulación de la Expresión Génica/efectos de los fármacos , Homeostasis/genética , Humanos , Transducción de Señal/genética , Factores de Transcripción/metabolismo , Transcripción Genética/genéticaRESUMEN
Focusing on problems existing in track irregularity time series data quality, this paper first presents abnormal data identification, data offset correction algorithm, local outlier data identification, and noise cancellation algorithms. And then proposes track irregularity time series decomposition and reconstruction through the wavelet decomposition and reconstruction approach. Finally, the patterns and features of track irregularity standard deviation data sequence in unit sections are studied, and the changing trend of track irregularity time series is discovered and described.
