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. 2019 Nov 9;20(22):5600. doi: 10.3390/ijms20225600

Figure 1.

Figure 1

Micro RNA (miRNA) mechanisms for mRNA translation, regulation, and therapeutic intervention. (A) miRNA normal function. In mammals, the interaction between miRNA (in blue) and mRNA targets trigger different mechanisms for transcript regulation through the RISC complex in order to achieve normal cellular protein levels (pink circles) [36,37]. (B) Causes of miRNA dysregulation. Alterations in miRNA biogenesis, editing, or in its biological stability may cause pathological upregulation or downregulation, which leads to decreased (green arrow) or increased (red arrow) target transcript translation regulation and final protein levels (pink circles), respectively [36]. (C) Illustration of miRNA-based technologies [36,37,59]. There are two main strategies of miRNA intervention depending on what is needed with regard to miRNA level correction. (Upper panel in C) When a miRNA is upregulated, inhibition is conducted by using antimiR products (in red) after miRNA-targeting drug development. Different types of antimiR products exist based on their mechanism of action. AntagomiR synthetic molecules are antisense oligonucleotides (ASOs) perfectly complementary to the specific miRNA target. A second strategy is the use of blockmiRs, which are designed to have a sequence that is complementary to one of the mRNA sequences that serve as a binding site for a microRNA. Upon binding, blockmiRs sterically block the microRNA from binding to the same site, which prevents degradation or transcription inhibition of the target. A third approach for direct miRNA binding and enhanced levels of inhibition involves the use of miRNA sponges. Sponges contain several tandemly arranged miRNA target sequences (same or different ones) usually embedded in the 3’UTR of a reporter gene for assessing the activity [60]. (Lower panel in C) miRNA replacement is conducted to restore its function by introducing a miRNA mimic product (in green) and, thus, following miRNA-based drug development. Micro-RNA mimics are synthetic double-stranded biomolecules that contain one strand with the same sequence and chemistry of the lacking miRNA and a second complementary strand that contains chemical modifications used for the delivery and protection of the mimic.