microRNAs at the synapse

• Published in: Nature reviews. Neuroscience Vol. 10; no. 12; pp. 842 - 849
• Main Author: Schratt, Gerhard
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2009; Nature Publishing Group
• Subjects: Animal Genetics and Genomics; Animals; Behavioral Sciences; Biochemistry. Physiology. Immunology; Biological and medical sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Dendrites - metabolism; Dendrites - ultrastructure; Fundamental and applied biological sciences. Psychology; Gene expression; Humans; Invertebrates; Localization; MicroRNAs; MicroRNAs - genetics; MicroRNAs - physiology; Mollusca; Nervous System Diseases - genetics; Nervous System Diseases - physiopathology; Neurobiology; Neuronal Plasticity - physiology; Neurosciences; Physiological aspects; Physiology. Development; Proteins; review-article; RNA; RNA Processing, Post-Transcriptional - genetics; RNA Processing, Post-Transcriptional - physiology; Synapses; Synapses - genetics; Synapses - physiology; Synapses - ultrastructure; Vertebrates: nervous system and sense organs; United States; Ability; Memory disorder; Synapse; Translation; Cognitive disorder; Modulation; Plasticity; Nervous system; Review
• ISSN: 1471-003X; 1471-0048; 1471-0048; 1469-3178
• DOI: 10.1038/nrn2763

Key Points MicroRNAs (miRNAs) are an extensive class of small non-coding RNAs that act as post-transcriptional regulators of gene expression in most cell types, including neurons. In animals, miRNAs mostly regulate gene expression at the level of mRNA translation through a mechanism that is still controversial. A subset of neuronal miRNAs are localized in the synaptodendritic compartment, where they participate in the local control of protein synthesis during synapse development and plasticity. Currently, more than 20 different miRNAs have been identified in dendrites of vertebrate neurons, but this is probably just the tip of the iceberg. The ability of miRNAs to regulate neuronal mRNA translation is itself subject to activity-dependent control. Neural activity controls miRNA transcription, subcellular localization and processing and the function of miRNA-associated multiprotein complexes. During the early stages of synaptogenesis, miRNA-regulated mechanisms are involved in the growth, remodelling and targeting of dendrites in both vertebrate and invertebrate model systems. The initial formation of synaptic contacts seems to be independent of miRNA activity. At least two miRNAs, miR-134 and miR-138, regulate the morphology of dendritic spines, the major sites of excitatory synaptic transmission in the vertebrate brain. miRNA-regulated pathways that are relevant for spine plasticity seem to converge on the actin cytoskeleton. Examples of a function of miRNAs in synaptic plasticity relevant to learning and memory have now been provided by several studies from invertebrates ( Caenorhabditis elegans , Drosophila melanogaster and Aplysia californica ). The miRNA-dependent regulation of important plasticity proteins, such as the neurotransmitter receptors CAMKII and CREB, might underlie this function. Several forms of higher-order processing, such as regulation of the circadian clock and neuroadaptations to drugs of abuse, have been shown to be influenced by miRNA activity. However, the relevance of miRNAs for synaptic plasticity in the mammalian system in vivo is yet to be determined. Several neuronal miRNA targets have been implicated in neurological diseases that are connected to synaptic dysfunction, for example autism-spectrum disorders and mental retardation. Impaired miRNA-dependent fine-tuning of synaptic proteins could result in defective neuronal homeostasis, a hallmark of these diseases. MicroRNAs are emerging as key modulators of post-transcriptional gene regulation in the synaptodendritic compartment. Here, Schratt reviews recent studies showing that neural activity controls microRNA transcription, subcellular localization, processing and function, and discusses the relevance of microRNAs for synapse development and plasticity. MicroRNAs (miRNAs) are emerging as key modulators of post-transcriptional gene regulation in a plethora of tissues, including the nervous system. Recent evidence points to a widespread role for neural miRNAs at various stages of synaptic development, including dendritogenesis, synapse formation and synapse maturation. Furthermore, studies from invertebrates indicate that miRNAs might contribute to the control of synapse function and plasticity in the adult. Key features of synapse-relevant miRNAs include their ability to regulate mRNA translation locally in the synaptodendritic compartment and the modulation of their expression and function by neuronal activity. The potentially huge impact of miRNA-based mechanisms on higher-order processing, memory and neuropsychiatric disorders in vertebrates is just starting to be recognized.