miRNA的生物形成及调控基因表达机制

微RNA(microRNA,miRNA)通过调节靶基因的表达水平影响细胞分化、增殖、凋亡等特性,在生物的生长发育和疾病发生发展中发挥重要的作用。将miRNA用于基因功能研究,药物靶点验证,基因治疗等领域有非常好的前景。揭示miRNA的生成和加工过程以及miRNA调节靶基因基因表达水平的作用机制对于阐述miRNA在生理病理过程中的作用有重要意义。因此,本文对miRNA的发生,成熟以及作用机制的研究进展作综述。     

血清microRNA——一种非侵入性的肿瘤标志物

microRNA(miRNA)是一类自然形成的非编码小RNA,不少miRNA分子已被证实与癌症的生成有关联。近期的研究发现人血清中稳定存在一定水平的miRNA,并且血清miRNA表达谱的变化与多种肿瘤的发生、发展具有明确的相关性,说明血清miRNA可以作为肿瘤临床诊断和预后评估的分子标志物。因此,特定的血清miRNA表达谱可以构成识别癌症与其他疾病的"指纹",为癌症及其他疾病的诊断提供一种新的非侵入性的检测方法,同时,该技术还可用于肿瘤分类、预后判断、手术疗效监测及疾病复发预测等领域,并可能带来未来临床医学上的变革。     

microRNAs在肝病中的研究进展

非编码小分子RNA(miRNA)调节肝脏生物学功能,大量实验表明,小分子RNA(miRNA)对肝脏病理学中有作用。本文概述了miRNA在肝炎、肝硬化肝病领域的进展。microRNA-122是肝细胞中最丰富的微小RNA,在丙型肝炎病毒复制中起着非常明确的作用。实验数据显示,microRNA-122亦可作为一种可行性的靶向治疗。microRNA-122在其他肝脏疾病中亦有作用。大量研究证明,与肝炎有关的其他类型miRNA的重要调节潜力与酒精性肝炎、代谢综合征和自身免疫过程有关。此外,在动物模型和人类研究中,miRNA系列与肝脏纤维化进程有关联。miRNA在肝脏中的功能与细胞分布重要性以及miRNA潜在地作为细胞与器官联系纽带,循环miRNA作为肝损伤、肝癌疾病早期和进展的生物学标志,这些是值得我们讨论的。重要的是:miRNA在肝脏中的调节作用,代表着未来肝病治疗医疗技术中的一种新方法。     

药用植物microRNA研究现状与展望

microRNA(miRNA)是一类由内源基因编码的长度约为22个核苷酸的非编码单链RNA分子,通过切割靶mRNA和抑制mRNA翻译,可在动植物中发挥重要的调控作用。自2002年首次出现植物mi RNA的报道后,植物miRNA的研究迅速成为植物分子生物学领域的研究热点。综述了植物miRNA的生物形成途径和作用机制,重点概述了药用植物中miRNA的研究现状,并对该领域未来的研究方向进行展望,以期为今后药用植物中miRNA的研究提供参考。     

生物信息学在植物miRNA研究中的应用

植物miRNA的研究已经从小规模实验向大规模计算分析方向发展,生物信息学的应用成为当前植物miRNA研究的热点问题。本文回顾了最近几年生物信息学在植物miRNA研究中取得的最新进展,简要介绍了植物miRNA的形成及其作用方式,重点对植物miRNA的计算识别、靶基因预测、启动子分析方法进行了讨论,并对相关的数据库资源进行了总结,最后展望了该领域研究的发展方向,将为植物miRNA的计算研究提供理论指导。     

生物信息学预测植物miRNAs的方法

MicroRNA又称miRNA,是一类广泛存在于动植物体内、大小为21~25nt左右的内源性非编码单链小分子RNA。在植物体中,miRNA主要负责调控转录后基因的表达,在机体发育、生长和应答胁迫方面发挥着重要的调节作用。近年来,miRNA已成为分子生物学领域的研究热点。本文介绍了几种发现和研究miRNA的方法,重点阐述了生物信息学预测miRNA方法的流程和策略,并对各过程中采用的方法及信息学软件的优劣性进行比较和分析,为预测miRNA提供新的思路。     

单细胞真核生物的miRNA系统及其进化意义

miRNA 系统在高等多细胞真核生物中得到了广泛深入的研究。近年来,人们在单细胞真核生物上的miRNA研究也取得了重要进展。这不仅丰富了人们对miRNA在整个生物界中的认识,更重要的是对于揭示miRNA这一表达调节系统是如何在生物界中起源进化的问题具有重要意义。该文结合作者在最低等单细胞真核生物——贾第虫上的研究结果,对该领域的研究进展作一概述,并对有关miRNA这一系统的起源进化问题进行了探讨。     

miRNA qPCR检测方法研究进展及其应用

miRNA是目前国际研究的热点领域之一,而miRNA表达检测是miRNA研究的基础内容。针对miRNA序列短小的特点,开发出了多种检测方法,其中miRNA qPCR定量检测是应用最广泛的方法。就miRNA抽提,miRNA qPCR定量检测原理及miRNA qPCR定量检测流程包括引物设计、反应体系设置、内参基因筛选等方面进行了深入探讨,并对miRNA定量检测研究方法的发展趋势进行了展望,以期为研究者进行miRNA qPCR定量检测提供参考。     

microRNA与结核病诊断的研究进展

microRNA(miRNA)是一类存在于真核细胞中的非编码小RNA,可以调控基因转录后表达。人体中30%以上的基因都受miRNA的调控,同时miRNA还可作为不同生理和病理状态的分子标记。尽管已经在各种生物中预测并证实了数百种miRNA,但miRNA及其靶基因的明确作用机制和功能尚不完全明了。许多研究表明,miRNA与肺部疾病感染的发生、发展及转化有着密切的关联。miRNA在肺部疾病的正负调节功能为细菌性肺部疾病的诊断和治疗提供了新方向。我们简述了miRNA在潜伏性肺结核病和活动性肺结核病诊断领域的研究进展。     

飞蝗两型small RNA转录组的鉴定比较

中国科学院动物研究所农业虫鼠害综合治理研究国家重点实验室康乐研究组应用高通量测序的方法在飞蝗中发现了大量的small RNA。研究人员通过与其它昆虫small RNA的比对发现了50种保守的miRNA,并且发展了一种新的方法在没有基因组序列的前提下挖掘飞蝗特有的miRNA,发现了大约185种飞蝗特有的miRNA candidates。     

miRNAs与药物成瘾

药物成瘾是一种慢性复发性脑病,主要表现为不可控制的对药物持续渴求和戒断后的高复吸。目前观点认为,成瘾是中脑腹侧被盖（ventral tegmental area,VTA）到伏隔核（nucleus accumbens,NAc）脑区多巴胺能奖赏通路中神经可塑性发生改变而导致的一种神经精神疾病。基因表达变化在神经可塑性中发挥着重要作用,但成瘾药物导致相关脑区结构和功能改变的机制还不甚清楚。微小RNAs（microRNAs,miRNAs）是一类非编码RNA,主要通过结合靶基因mRNA 3′非翻译区（3′untranslated region,3′UTR）,在转录后水平阻断其翻译成蛋白质或触发其不稳定而降解。越来越多的研究证实,miRNAs参与调节成瘾相关神经可塑性的变化。本文较系统地阐述miRNAs在药物成瘾中的作用研究进展,将为深入阐明药物成瘾的机制以及药物成瘾临床有效干预和诊治提供新思路。     

MicroRNAs regulate synaptic plasticity underlying drug addiction

Chronic use of drugs of abuse results in neurochemical, morphological and behavioral plasticity that underlies the emergence of compulsive drug seeking and vulnerability to relapse during periods of attempted abstinence. Identifying and reversing addiction‐relevant plasticity is seen as a potential point of pharmacotherapeutic intervention in drug‐addicted individuals. Despite considerable advances in our understanding of the actions of drugs of abuse in the brain, this information has thus far yielded few novel treatment options addicted individuals. MicroRNAs are small noncoding RNAs that can each regulate the translation of hundreds to thousands of messenger RNAs. The highly pleiotropic nature of miRNAs has focused attention on their contribution to addiction‐relevant structural and functional plasticity in the brain and their potential utility as targets for medications development. In this review, we discuss the roles of miRNAs in synaptic plasticity underlying the development of addiction and then briefly discuss the possibility of using circulating miRNA as biomarkers for addiction.     

microRNA-Seq reveals cocaine-regulated expression of striatal microRNAs

MicroRNAs (miRNAs) are small RNAs that modulate gene expression by binding target mRNAs. The hundreds of miRNAs expressed in the brain are critical for synaptic development and plasticity. Drugs of abuse cause lasting changes in the limbic regions of the brain that process reward, and addiction is viewed as a form of aberrant neuroplasticity. Using next-generation sequencing, we cataloged miRNA expression in the nucleus accumbens and at striatal synapses in control and chronically cocaine-treated mice. We identified cocaine-responsive miRNAs, synaptically enriched and depleted miRNA families, and confirmed cocaine-induced changes in protein expression for several predicted synaptic target genes. The miR-8 family, known for its roles in cancer, is highly enriched and cocaine regulated at striatal synapses, where its members may affect expression of cell adhesion molecules. Synaptically enriched cocaine-regulated miRNAs may contribute to long-lasting drug-induced plasticity through fine-tuning regulatory pathways that modulate the actin cytoskeleton, neurotransmitter metabolism, and peptide hormone processing.     

Differential expression profiles of plasma exosomal microRNAs in dilated cardiomyopathy with chronic heart failure

As one of the most prevalent heritable cardiovascular diseases, dilated cardiomyopathy (DCM) induces cardiac insufficiency and dysfunction. Although genetic mutation has been identified one of the causes of DCM, the usage of genetic biomarkers such as RNAs for DCM early diagnosis is still being overlooked. In addition, the alternation of RNAs could reflect the progression of the diseases, as an indicator for the prognosis of patients. Therefore, it is beneficial to develop genetic based diagnostic tool for DCM. RNAs are often unstable within circulatory system, leading to the infeasibility for clinical application. Recently discovered exosomal miRNAs have the stability that is then need for diagnostic purpose. Hence, fully understanding of the exosomal miRNA within DCM patients is vital for clinical translation. In this study, we employed the next generation sequencing based on the plasma exosomal miRNAs to comprehensively characterize the miRNAs expression in plasma exosomes from DCM patients exhibiting chronic heart failure (CHF) compared to healthy individuals. A complex landscape of differential miRNAs and target genes in DCM with CHF patients were identified. More importantly, we discovered that 92 differentially expressed miRNAs in DCM patients undergoing CHF were correlated with several enriched pathways, including oxytocin signalling pathway, circadian entrainment, hippo signalling pathway-multiple species, ras signalling pathway and morphine addiction. This study reveals the miRNA expression profiles in plasma exosomes in DCM patients with CHF, and further reveal their potential roles in the pathogenesis of it, presenting a new direction for clinical diagnosis and management of DCM patients with CHF.     

Comparative genomic analysis reveals evolutionary characteristics and patterns of microRNA clusters in vertebrates

MicroRNAs (miRNAs) are a class of small non-coding RNAs that can play important regulatory roles in many important biological processes. Although clustering patterns of miRNA clusters have been uncovered in animals, the origin and evolution of miRNA clusters in vertebrates are still poorly understood. Here, we performed comparative genomic analyses to construct 51 sets of orthologous miRNA clusters (SOMCs) across seven test vertebrate species, a collection of miRNA clusters from two or more species that are likely to have evolved from a common ancestral miRNA cluster, and used these to systematically examine the evolutionary characteristics and patterns of miRNA clusters in vertebrates. We found that miRNA clusters are continuously generated, and most of them tend to be conserved and maintained in vertebrate genomes, although some adaptive gains and losses of miRNA cluster have occurred during evolution. Furthermore, miRNA clusters appeared relatively early in the evolutionary history might suffer from more complicated adaptive gain-and-loss than those young miRNA clusters. Detailed analysis showed that genomic duplication events of ancestral miRNAs or miRNA clusters are likely to be major driving force and apparently contribute to origin and evolution of miRNA clusters. Comparison of conserved with lineage-specific miRNA clusters revealed that the contribution of duplication events for the formation of miRNA cluster appears to be more important for conserved miRNA clusters than lineage-specific. Our study provides novel insights for further exploring the origins and evolution of miRNA clusters in vertebrates at a genome scale.     

Selection on Synonymous Sites for Increased Accessibility around miRNA Binding Sites in Plants

Synonymous codons are widely selected for various biological mechanisms in both prokaryotes and eukaryotes. Recent evidence suggests that microRNA (miRNA) function may affect synonymous codon choices near miRNA target sites. To better understand this, we perform genome-wide analysis on synonymous codon usage around miRNA target sites in four plant genomes. We observed a general trend of increased site accessibility around miRNA target sites in plants. Guanine-cytosine (GC)-poor codons are preferred in the flank region of miRNA target sites. Within-genome analyses show significant variation among miRNA targets in species. GC content of the target gene can partly explain the variation of site accessibility among miRNA targets. miRNA targets in GC-rich genes show stronger selection signals than those in GC-poor genes. Gene's codon usage bias and the conservation level of miRNA and its target also have some effects on site accessibility, but the expression level of miRNA or its target and the mechanism of miRNA activity do not contribute to site accessibility differences among miRNA targets. We suggest that synonymous codons near miRNA targets are selected for efficient miRNA binding and proper miRNA function. Our results present a new dimension of natural selection on synonymous codons near miRNA target sites in plants, which will have important implications of coding sequence evolution.     

植物microRNA的保守性及其分布的分析

MicroRNA(miRNA)是真核生物中具有重要调控作用的小分子非编码RNA。本文对miRNA官网miRBase数据库Release 22.1中隶属于植物界的绿藻门、苔藓植物门、蕨类植物门、裸子植物门、被子植物门共计82个物种的miRNA进行了统计分析。miRBase共收录植物miRNA 前体8 615个,成熟miRNA 10 414条,隶属于2 892个miRNA家族。绿藻门miRNA与其他4个门miRNA无同源性;对其他4个门植物miRNA的保守性进行研究,发现存在于2个植物门的miRNA家族有26个,属于中度保守miRNA家族;14个miRNA家族存在于3个及3个以上植物门中,属于高度保守miRNA家族,其中7个miRNA家族系苔藓、蕨类、裸子和被子植物共有,是植物中最保守的miRNA。分析表明,超过30个miRNA家族的植物有35种。进一步对40个中度或者高度保守miRNA在35种植物中的分布进行研究,发现miRNA家族及其成员在物种间的分布存在较大的差异。这些分布上的差异一方面反映不同植物中miRNA的研究深度不同,另一方面也反映出miRNA在植物进化过程中的适应性调整。研究不同植物中miRNA家族的分布,可在miRNA水平为植物早期进化同源性的研究提供分子依据。     

植物miRNA的进化

鉴于miRNA在植物基因表达调控中的重要作用, 人们已经开展对植物miRNA的预测、鉴定、功能和进化等方面的研究。随着许多模式植物基因组测序的完成, miRNA的基因组学和进化信息的整合为miRNA的起源和进化研究提供了越来越多的证据和假说, 然而尚未见关于植物miRNA进化方面的系统报道。文章从miRNA的起源以及相应的几种假说、miRNA的产生和消亡、miRNA的功能进化等几方面来分析和综述植物miRNA进化的研究进展。