A Novel Strategy for Regulating mRNA’s Degradation via Interfering the AUF1’s Binding to mRNA

Abstract

The study on the mechanism and kinetics of mRNA degradation provides a new vision for chemical intervention on protein expression. The AU enrichment element (ARE) in mRNA 3′-UTR can be recognized and bound by the ARE binding protein (AU-rich Element factor (AUF1) to recruit RNase for degradation. In the present study, we proposed a novel strategy for expression regulation that interferes with the AUF1-RNA binding. A small-molecule compound, JNJ-7706621, was found to bind AUF1 protein and inhibit mRNA degradation by screening the commercial compound library. We discovered that JNJ-7706621 could inhibit the expression of AUF1 targeted gene IL8, an essential pro-inflammatory factor, by interfering with the mRNA homeostatic state. These studies provide innovative drug design strategies to regulate mRNA homeostasis.

Silk‐based conductive materials for smart biointerfaces

“…On the other hand, for the fabrication of porous sponge scaffolds, a conventional manufacturing method is freeze‐drying technology. By controlling the SF concentration, pH, and freezing temperature, the pore structure within the sponge scaffold, such as pore size and porosity, can be efficiently tuned 47,48 . Besides freeze‐drying technology, salt leaching and gas foaming techniques are other methods to prepare porous sponge scaffolds 49 .…”

Silk Fibroin Combined with Electrospinning as a Promising Strategy for Tissue Regeneration

“…Silk II predominantly comprises β ‐sheets, which are stable in structure and insoluble in water, not easily degraded by acids, alkalis, and enzymes and have high mechanical strength. [ 28,36 ] The silk I structure can be transformed into silk II under the influence of temperature, organic solvent, pH value, metal ions, physical shear, electromagnetic field, and other conditions. Accordingly, the researchers were able to regulate the water solubility and degradation rate of SF by regulating the proportion of different crystal structures in SF.…”

“…[26,27] SF accounts for approximately 70%-80% of the total weight of silk, while sericin accounts for approximately 20%-30%. [28,29] The extraction of SF is by first removing sericin through degumming treatment, mainly utilizing the water solubility of sericin, which can be completely dissolved by placing it in a heated alkaline solution. [30] The degummed fibroin retains the structure of its large filamentous fibers and is commonly dissolved in a lithium bromide solution or a calcium chloride/ethanol/water ternary solvent.…”