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. 2021 Oct 6;10(10):2679. doi: 10.3390/cells10102679

Figure 1.

Figure 1

Overview of the miRNA pathway and its dysregulation in 22q11DS and idiopathic SCZ. The miRNA pathway begins when transcription produces a pri-miRNA, which undergoes sequential processing into a pre-miRNA by the Microprocessor and DICER to produce a mature miRNA. The mature miRNA is then loaded into an AGO protein complex to produce an active RNA-silencing complex (RISC), which binds to mRNAs containing complementary sequences and promotes mRNA degradation and/or inhibits protein synthesis. Current models of 22q11DS, which is associated with elevated SCZ risk, suggest that DGCR8 haploinsufficiency impairs Microprocessor activity, leading to widespread downregulation of miRNAs. In contrast, several studies suggest that several components of the miRNA pathway (i.e., DGCR8, DROSHA, and DICER1 mRNAs) are upregulated in idiopathic SCZ. Furthermore, in patients with idiopathic SCZ, overrepresentation of CNVs affecting miRNA genes (outside of the 22q11.2 region) and dysregulated miRNA levels in postmortem brain suggest that both up- and downregulation of miRNAs may contribute to SCZ risk. Abbreviations: AGO, Argonaute protein; CNV, copy number variant; RNA pol II, RNA polymerase II.