microRNAs in neurons: manifold regulatory roles at the synapse

The regulation of synapse formation and plasticity in the developing and adult brain underlies a complex interplay of intrinsic genetic programs and extrinsic factors. Recent research identified microRNAs (miRNAs), a class of small non-coding RNAs, as a new functional layer in this regulatory network. Within only a few years, a network of synaptic miRNAs and their target genes has been extensively characterized, highlighting the importance of this mechanism for synapse development and physiology. Very recent data further provide insight into activity-dependent regulation of miRNAs, thereby connecting miRNAs with adaptive processes of neural circuits. First direct links between miRNA dysfunction and synaptic pathologies are emerging, raising the interest in these molecules as potential biomarkers and therapeutic targets in neurological disorders.     

Activity-Dependent Bidirectional Regulation of GAD Expression in a Homeostatic Fashion Is Mediated by BDNF-Dependent and Independent Pathways

Homeostatic synaptic plasticity, or synaptic scaling, is a mechanism that tunes neuronal transmission to compensate for prolonged, excessive changes in neuronal activity. Both excitatory and inhibitory neurons undergo homeostatic changes based on synaptic transmission strength, which could effectively contribute to a fine-tuning of circuit activity. However, gene regulation that underlies homeostatic synaptic plasticity in GABAergic (GABA, gamma aminobutyric) neurons is still poorly understood. The present study demonstrated activity-dependent dynamic scaling in which NMDA-R (N-methyl-D-aspartic acid receptor) activity regulated the expression of GABA synthetic enzymes: glutamic acid decarboxylase 65 and 67 (GAD65 and GAD67). Results revealed that activity-regulated BDNF (brain-derived neurotrophic factor) release is necessary, but not sufficient, for activity-dependent up-scaling of these GAD isoforms. Bidirectional forms of activity-dependent GAD expression require both BDNF-dependent and BDNF-independent pathways, both triggered by NMDA-R activity. Additional results indicated that these two GAD genes differ in their responsiveness to chronic changes in neuronal activity, which could be partially caused by differential dependence on BDNF. In parallel to activity-dependent bidirectional scaling in GAD expression, the present study further observed that a chronic change in neuronal activity leads to an alteration in neurotransmitter release from GABAergic neurons in a homeostatic, bidirectional fashion. Therefore, the differential expression of GAD65 and 67 during prolonged changes in neuronal activity may be implicated in some aspects of bidirectional homeostatic plasticity within mature GABAergic presynapses.     

Neuronal activity regulates hippocampal miRNA expression

Neuronal activity regulates a broad range of processes in the hippocampus, including the precise regulation of translation. Disruptions in proper translational control in the nervous system are associated with a variety of disorders that fall in the autistic spectrum. MicroRNA (miRNA) represent a relatively recently discovered player in the regulation of translation in the nervous system. We have conducted an in depth analysis of how neuronal activity regulates miRNA expression in the hippocampus. Using deep sequencing we exhaustively identify all miRNAs, including 15 novel miRNAs, expressed in hippocampus of the adult mouse. We identified 119 miRNAs documented in miRBase but less than half of these miRNA were expressed at a level greater than 0.1% of total miRNA. Expression profiling following induction of neuronal activity by electroconvulsive shock demonstrates that most miRNA show a biphasic pattern of expression: rapid induction of specific mature miRNA expression followed by a decline in expression. These results have important implications into how miRNAs influence activity-dependent translational control.     

植物逆境miRNA研究进展

包括生物和非生物在内的多种逆境胁迫是植物正常生长和作物产量提高的重要限制性因素。植物在长期的进化过程中, 通过诱导表达某些抵御或防卫途径的关键基因来实现对胁迫的响应。研究表明, 逆境胁迫不仅会诱导植物蛋白质编码基因的表达, 也会诱导一些非蛋白质编码基因的表达, 这类非蛋白质编码基因的表达产物在植物的生长、发育和应对逆境胁迫等过程中起到重要的调控作用。miRNA(小分子RNA)就是这类非蛋白质编码基因产物中的重要类群, 研究发现, 多种逆境均会诱导miRNA的产生, 其作用是通过引导目的基因mRNA的降解和阻止翻译过程来调控靶基因, 最终通过形态或生理上的变化达到对逆境的适应。文章主要对植物逆境胁迫下miRNA的研究, 特别是逆境胁迫诱导miRNA的产生、靶基因调控以及miRNA在植物适应逆境胁迫过程中的作用进行了综述, 同时, 文章还对在逆境胁迫下植物miRNA的研究方法进行了初步的探讨。     

MiRNA 与皮肤伤口愈合

MiRNA是真核生物体内约由22个核苷酸组成的内源性非编码单链RNA,可调节基因转录。它通过其5’非翻译区(UTR)与目标mRNA的3’端非翻译区相结合,从而抑制后者的转录后翻译和降解,进而调节一系列生物学过程,包括生物体生长、发育和疾病等。研究表明,miRNA在干细胞分化、肿瘤形成、血管发生、内耳形成等过程中均发挥重要作用,已成为调节生物学过程的核心因子。伤口愈合是一个与多种类型细胞、细胞因子及细胞外基质相关的过程,它受机体多种因素紧密调控。伤口愈合过程一般被分为三个阶段:炎症反应期,肉芽生长期和组织重建期。已有大量证据证实miRNA在皮肤创伤愈合过程中发挥重要作用,并且miRNA在不同的愈合阶段发挥不同的作用。本文就miRNA在皮肤形态、胎儿无痕愈合及成人伤口愈合各环节中的作用做一综述。     

A Comprehensive Review of Dysregulated miRNAs Involved in Cervical Cancer

MicroRNAs(miRNAs) have become the center of interest in oncology. In recent years, various studies have demonstrated that miRNAs regulate gene expression by influencing important regulatory genes and thus are responsible for causing cervical cancer. Cervical cancer being the third most diagnosed cancer among the females worldwide, is the fourth leading cause of cancer related mortality. Prophylactic human papillomavirus (HPV) vaccines and new HPV screening tests, combined with traditional Pap test screening have greatly reduced cervical cancer. Yet, thousands of women continue to be diagnosed with and die of this preventable disease annually. This has necessitated the scientists to ponder over ways of evolving new methods and chalk out novel treatment protocols/strategies. As miRNA deregulation plays a key role in malignant transformation of cervical cancer along with its targets that can be exploited for both prognostic and therapeutic strategies, we have collected and reviewed the role of miRNA in cervical cancer. A systematic search was performed using PubMed for articles that report aberrant expression of miRNA in cervical cancer. The present review provides comprehensive information for 246 differentially expressed miRNAs gathered from 51 published articles that have been implicated in cervical cancer progression. Of these, more than 40 miRNAs have been reported in the literature in several instances signifying their role in the regulation of cancer. We also identified 40 experimentally validated targets, studied the cause of miRNAs dysregulation along with its mechanism and role in different stages of cervical cancer. We also identified and analysed miRNA clusters and their expression pattern in cervical cancer. This review is expected to further enhance our understanding in this field and serve as a valuable reference resource.     

Thinking about RNA? MicroRNAs in the brain

MicroRNAs (miRNAs) are a recently discovered class of small RNA molecules implicated in a wide range of diverse gene regulatory mechanisms. Interestingly, numerous miRNAs are expressed in a spatially and temporally controlled manner in the nervous system. This suggests that gene regulation networks based on miRNA activities may be particularly relevant in neurons. Recent studies show the involvement of RNA-mediated gene silencing in neurogenesis, neural differentiation, synaptic plasticity, and neurologic and psychiatric diseases. This review focuses on the roles of miRNAs in the gene regulation of the nervous system.