Figure 5 : The regulation of mRNA stability by a sense oligonucleotide using NATRE technology.

Schematic models of the regulation of mRNA stability by a sense oligonucleotide are shown. The sense oligonucleotide acts as an
effector to control mRNA levels through an asRNA-mediated post-transcriptional regulation mechanism.

(A) A sense oligonucleotide down-regulates mRNA levels. When mRNA interacts with asRNA and a stabilizing protein, such as HuR, the mRNA is stabilized. When a sense oligonucleotide is introduced, it competes with mRNA to block asRNA-mRNA interactions. This inhibition results in the degradation of the mRNA (broken line) because the stabilizing protein is dissociated from the mRNA. Down-regulation of the mRNA level occurs, such as when sense oligonucleotides corresponding to iNOS [7] and IL-23A mRNA were used.

(B) A sense oligonucleotide up-regulates mRNA levels. The mRNA becomes unstable when a destabilizing protein, such as TTP, binds to the mRNA. The sense oligonucleotide competes with the mRNA to block the asRNA-mRNA interactions, resulting in the dissociation of the destabilizing protein from mRNA. Up-regulation of mRNA levels occurs, such as when sense oligonucleotides corresponding to CCL2, CCL20, CX3CL1, CD69, and NF-κB p65 mRNA were used.

Nishizawa et al.  2012 1:10DOI : 10.7243/2050-0874-1-10