MicroRNAs as Effectors of Brain Function

MicroRNAs (miRNAs) are a recently discovered family of small, genome-encoded endogenous RNAs that are transcribed but are not translated into proteins. Early studies in Ceanorhabditis elegans revealed that an endogenous small RNA (lin-4) regulated translation of lin-14, a protein required for postembryonic development, through an RNA–RNA interaction.1 Small RNAs were then shown to mediate gene-silencing via a mechanism known as RNA interference (RNAi).2 Fire and Mello2 were awarded the Nobel Prize in Physiology or Medicine in 2006 for the discovery of RNAi. The term miRNA was introduced in a series of back-to-back Science articles in 2001.3–5 MiRNA genes produce primary miRNA transcripts which contain at least one, but possibly more, ≈70 nucleotide hairpin loops. These transcripts are transported into the cytoplasm where they are cleaved by the endonuclease Dicer into an imperfect duplex of 20 to 25 nucleotides. One strand of the duplex is degraded and the other mature miRNA binds to Dicer and forms a complex with argonaute proteins to form RNA-induced silencing complexes.6,7 Studies from several laboratories have revealed that the predominant role of miRNAs in RNA-induced silencing complexes is to regulate post-transcriptional gene expression by translational repression, mRNA cleavage, and mRNA decay initiated by miRNA-guided rapid deadenylation. However, emerging studies support that possible involvement of miRNAs in transcriptional and translational activation. Tremendous progress has been made in unraveling the complexities of miRNAs as meta-controllers of gene expression and their impact on cell development, survival, and function, yet miRNA research is still in its infancy. Given the enormous potential for miRNA studies to translate into novel therapeutic strategies for the diagnosis and treatment of many diseases, the quest to examine all aspects …