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The biogenesis and biological roles of tRNA-derived short RNAs
Chengjun Wang, Jia Wang, Mingze Wang, Yike Lu, Jizong Zhao
Journal of Translational Neuroscience. 2017, 2 (1): 1-9.
https://doi.org/10-3868/j.issn.2096-0689.2017.01.001
In recent years, next-generation sequencing (NGS) technologies targeting the microRNA (miRNA) transcriptome revealed the existence of tRNA-derived short RNAs: tRNA halves (tiRNAs) and tRNA-derived fragments (tRFs). These small RNAs represent a noveltype of small non-coding RNAs (sncRNAs), which are heterogeneous in size, nucleotide composition and biogenesis, and have been suggested to be involved in translation, cell proliferation, priming of viral reverse transcriptases, regulation of gene expression, modulation of the DNA damage response, tumor suppression and neurological disorders. Herein, we review the mechanism of their biogenesis and discuss in detail the regulatory roles they play in cell physiology. We also point out that the biological function of tRNA-derived short RNAs will be understood better as research moves forward, and that this knowledge will find its way into clinical application in the near future.
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Focusing on neuronal cell-type specific mechanisms for brain circuit organization, function and dysfunction
Lu Li
Journal of Translational Neuroscience. 2017, 2 (1): 28-35.
https://doi.org/10-3868/j.issn.2096-0689.2017.01.004
Mammalian brain circuits consist of dynamically interconnected neurons with characteristic morphology, physiology, connectivity and genetics which are often called neuronal cell types. Neuronal cell types have been considered as building blocks of brain circuits, but knowledge of how neuron types or subtypes connect to and interact with each other to perform neuralcomputation is still lacking. Such mechanistic insights are critical not only to our understanding of normal brain functions, such as perception, motion and cognition, but
also to brain disorders including Alzheimer’s disease, Schizophrenia and epilepsy, to name a few. Thus it is necessary to carry out systematic and standardized studies on neuronal cell-type specific mechanisms for brain circuit organization and function, which will provide good opportunities to bridge basic and clinical research. Here based on recent technology advancements,we discuss the strategy to target and manipulate specific populations of neurons in vivo to provide unique insights on how neuron types or subtypes behave, interact, and generate emergent properties in a fully connected brain network. Our approach is highlighted by combining
transgenic animal models, targeted electrophysiology and imaging with robotics, thus complete and standardized mapping of in vivo properties of genetically defined neuron populations can be achieved in transgenic mouse models, which will facilitate the development of novel therapeutic strategies for brain disorders.
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Xenopus transgenic to screen candidate molecules favoring myelin repair
Abdelkrim Mannioui, David Du Pasquier, Bernard Zalc
Journal of Translational Neuroscience. 2017, 2 (1): 36-40.
https://doi.org/10-3868/j.issn.2096-0689.2017.01.005
To facilitate live imaging of demyelination and remyelination, we have generated a Xenopus laevis transgenic line, MBP-GFP-NTR, allowing conditional ablation of myelinating oligodendrocytes. In this line, the proximal portion of mouse myelin basic protein (MBP) regulatory sequence, specific to mature myelin-forming oligodendrocytes, drives the expression of a transgene protein formed by the GFP reporter fused to the Escherichia coli nitroreductase (NTR) selection enzyme. The NTR enzyme converts the innocuous prodrug metronidazole (MTZ) to a cytotoxin. The demyelination response of MBP-GFP-NTR tadpoles to MTZ is followed by spontaneous remyelination after cessation of MTZ treatment. Thanks to the transparency of tadpoles,these events can be monitored in vivo by two-photon imaging and easily quantified on a simple fluorescence macroscope. We have used the MBP-GFP-NTR model to screen in vivo molecules favoring remyelination. At the end of MTZ-induced demyelination, tadpoles were switched to water containing the compounds to be tested.After 3 days of treatment remyelination was assayed by counting the number of GFP+ oligodendrocytes per optic nerve. Using Crispr/Cas9 strategy, the target of the candidate molecule can be easily deleted in the MBPGFP-NTR line to examine the mechanism of action of the candidate molecule. Therefore the Xenopus laevis transgenic line, MBP-GFP-NTR, allowing conditional ablation of myelinating oligodendrocytes, constitutes a new medium-throughput screening platform for myelin repair therapeutics in demyelinating diseases.
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