A MicroRNA-Mediated Positive Feedback Regulatory Loop of the NF-{kappa}B Pathway in Litopenaeus vannamei [INNATE IMMUNITY AND INFLAMMATION]

In the evolutionarily conserved canonical NF-B pathway, degradation of the NF-B inhibitor IB in the cytoplasmic NF-B/IB complex allows the liberated NF-B to translocate into the nucleus to activate various target genes. The regulatory mechanism governing this process needs further investigation. In this study, a novel microRNA, temporarily named miR-1959, was first identified from an invertebrate Litopenaeus vannamei. miR-1959 targets the 3'-untranslated region of the IB homolog Cactus gene and reduces the protein level of Cactus in vivo, whereas the NF-B homolog Dorsal directly binds the miR-1959 promoter to activate its transcription. Therefore, miR-1959 mediates a positive feedback regulatory loop, in that Dorsal activates miR-1959 expression, and in turn, miR-1959 inhibits the expression of Cactus, further leading to enhanced activation of Dorsal. Moreover, miR-1959 regulates the expression of many antimicrobial peptides in vivo and is involved in antibacterial immunity. To our knowledge, it is the first discovery of a microRNA-mediated feedback loop that directly regulates the NF-B/IB complex. This positive feedback loop could collaborate with the known NF-B/IB negative loop to generate a dynamic balance to regulate the activity of NF-B, thus constituting an effective regulatory mechanism at the critical node of the NF-B pathway.

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from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/22IUSOh
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