视神经损伤
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Figure 1｜A schematic representation of miRNA synthesis.
miRNA are short (22 nucleotide) non-coding RNA that function to silence mRNA translation into proteins. Through a highly regulated sequence of cleavages and annealings performed by the proteins Dicer and Drosha, pri-miRNA are converted to pre-miRNA and finally mature miRNA (Zuzic et al., 2019). They act by guiding argonaute proteins, which form part of the RNA-induced silencing complex, to mRNA sequences partially complementary to the miRNA sequence. The targeted mRNA’s translational efficiently is subsequently reduced and may even be degraded completely (Figure 1). There are approximately 2500 miRNA that have been identified in humans and each miRNA can have hundreds of experimentally observed targets (and thousands of predicted targets), making their role in health and disease incredibly complicated and largely unknown (http://www.miRBase.org; http://mirdb.org; http://mirwalk.umm.uni-heidelberg.de). A subset of microRNA (about 400) is localized to mitochondria (John et al., 2020). An important consideration is the miRNA-mediated down-regulation of mRNA and subsequent reduction in translated protein does not inherently mean their role is to inhibit signaling pathways. Many signaling pathways are activated through miRNA-mediated inhibition of negative regulators. For example, the mTOR/PI3K/Akt pathway leads to the activation of discrete protein synthesis, cell growth, and regeneration. Activation of this pathway leads to axon regeneration. PTEN suppresses this pathway whereas PTEN knockdown activates this pathway and leads to significant regeneration and neuroprotection in models of retinal and spinal cord injury (Park et al., 2008). PTEN is interestingly the target of multiple miRNA including miR-214 (Bera et al., 2017), miR-1908 (Xia et al., 2015), miR-494 (Wang et al., 2010) and miR-21 (Sayed et al., 2010), and thus these miRNA would lead to the activation of the mTOR/PI3K/Akt pathway.