MicroRNAs (miRNAs) are a class of small, non-coding RNAs, about 22 nucleotides long that are important components of a highly conserved gene regulatory mechanism. Although abnormalities in miRNA-mediated gene regulation have been observed in a variety of human diseases, the study of miRNAs in psychiatric disorders and in normal neuronal development is still in its infancy. Individuals with 22q11.2 microdeletions are at high risk to develop schizophrenia. Here, we summarize recent findings from our laboratory using a mouse model of the human 22q11.2 locus, which led to the discovery of a previously unknown alteration in the biogenesis of miRNAs emerging as a result of the 22ql 1.2 micro-deletion. We review available evidence indicating that the abnormal miRNA biogenesis emerges due to haploinsufficiency of the Dgcr8 gene, which encodes for a RNA binding moiety of the "microprocessor" complex and contributes to the behavioral and neuronal deficits associated with the 22ql 1.2 microdeletion. To help interpret those findings in the context of the existing knowledge, we also outline our current knowledge about miRNA biogenesis and potential mode of action and summarize a number of current studies on the role of miRNAs in the developing and adult central nervous system, as well as on the emerging connections between miRNAs and neuropsychiatric diseases.
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