Interdisziplinäres Zentrum für Neurowissenschaften, SFB488 Junior Group, Universität Heidelberg, and Institut für Neuroanatomie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.
The development and function of the nervous system is orchestrated by a plethora of gene regulatory mechanisms. MicroRNAs (miRNAs), an abundant class of small non-coding RNAs, are emerging as important post-transcriptional regulators of gene expression in the brain. MiRNAs function at all stages of neuronal development, ranging from the initial specification of neuronal cell types to the formation and plasticity of synaptic connections between individual neurons. Moreover, links between miRNA dysfunction and neurological diseases become more and more apparent. The study of this novel layer of gene regulation therefore promises to enrich our knowledge of brain function and pathology.
"Post-transcription interference by microRNAs (miRNAs) is another epigenetic mechanism and has been implied in neurogenesis and synaptic plasticity (Fiore et al., 2008). However, several representative miRNAs influential for neurogenesis and synaptic plasticity including miR9, miR124a, and miR132 did not significantly change their expression levels following EE (Kuzumaki et al., 2011). "
[Show abstract][Hide abstract] ABSTRACT: It has been half a century since brain volume enlargement was first reported in animals reared in an enriched environment (EE). As EE animals show improved memory task performance, exposure to EE has been a useful model system for studying the effects of experience on brain plasticity. We review EE-induced neural changes in the cerebral cortex and hippocampus focusing mainly on works published in the recent decade. The review is organized in three large domains of changes: anatomical, electrophysiological, and molecular changes. Finally, we discuss open issues and future outlook towards better understanding of EE-induced neural changes.
"During the late embryonic stage, Dicer affects the survival and differentiation of cortical neural progenitor cells, leading to the deviant migration of cortical neurons 27. Ago, a part of the RNA-induced silencing complex 27, 28, also plays important roles in the CNS development. For example, neural tube closure is prevented in mice with Ago mutation 29. "
[Show abstract][Hide abstract] ABSTRACT: microRNAs (miRNAs) are a novel class of small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. miRNAs can modulate gene expression and thus play important roles in diverse neurobiological processes, such as cell differentiation, growth, proliferation and neural activity, as well as the pathogenic processes of spinal cord injury (SCI) like inflammation, oxidation, demyelination and apoptosis. Results from animal studies have revealed the temporal alterations in the expression of a large set of miRNAs following SCI in adult rats, and the expressional changes in miRNAs following SCI is bidirectional (increase or decrease). In addition, several miRNAs have distinct roles in prognosis of SCI (protective, detrimental and varied). Taken together, the existing evidence suggests that abnormal miRNA expression following SCI contributes to the pathogenesis of SCI, and miRNAs may become potential targets for the therapy of SCI.
International journal of biological sciences 09/2014; 10(9):997-1006. DOI:10.7150/ijbs.9058 · 4.51 Impact Factor
"In addition, individual miRNAs can regulate multiple mRNAs further complicating the gene regulatory networks of miRNAs. Therefore, dysregulation of miRNAs can have detrimental cellular consequences and has been associated with several human diseases ranging from metabolic and inflammatory disease to malignancy (Carè et al., 2007; Fiore et al., 2008; Krü tzfeldt and Stoffel, 2006; Lu et al., 2005; Poy et al., 2004). "
[Show abstract][Hide abstract] ABSTRACT: MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by binding to sequences within the 3' UTR of mRNAs. Because miRNAs bind to short sequences with partial complementarity, target identification is challenging. To complement the existing target prediction algorithms, we devised a systematic "reverse approach" screening platform that allows the empirical prediction of miRNA-target interactions. Using Drosophila cells, we screened the 3' untranslated regions (3' UTRs) of the Hedgehog pathway genes against a genome-wide miRNA library and identified both predicted and many nonpredicted miRNA-target interactions. We demonstrate that miR-14 is essential for maintaining the proper level of Hedgehog signaling activity by regulating its physiological target, hedgehog. Furthermore, elevated levels of miR-14 suppress Hedgehog signaling activity by cotargeting its apparent nonphysiological targets, patched and smoothened. Altogether, our systematic screening platform is a powerful approach to identifying both physiological and apparent nonphysiological targets of miRNAs, which are relevant in both normal and diseased tissues.
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