Evolutionarily conserved function of a viral microRNA

MicroRNAs (miRNAs) are potent RNA regulators of gene expression. Some viruses encode miRNAs, most of unknown function. The majority of viral miRNAs are not conserved, and whether any have conserved functions remains unclear. Here, we report that two human polyomaviruses associated with serious disease in immunocompromised individuals, JC virus and BK virus, encode miRNAs with the same function as that of the monkey polyomavirus simian virus 40 miRNAs. These miRNAs are expressed late during infection to autoregulate early gene expression. We show that the miRNAs generated from both arms of the pre-miRNA hairpin are active at directing the cleavage of the early mRNAs. This finding suggests that despite multiple differences in the miRNA seed regions, the primary target (the early mRNAs) and function (the downregulation of early gene expression) are evolutionarily conserved among the primate polyomavirus-encoded miRNAs. Furthermore, we show that these miRNAs are expressed in individuals diagnosed with polyomavirus-associated disease, suggesting their potential as targets for therapeutic intervention.     

miRNA介导PGR信号通路在雌性生殖功能调节中的作用机制

MicroRNA(miRNA)作为重要的后转录调节因子参与多种生理活动。孕酮(Progesterone,P4)是重要的甾类激素,通过结合特异性受体——孕酮受体(Progesterone receptors , PGR)发挥生理作用。PGR作为核受体超家族的一员参与调控生殖相关组织或非生殖相关组织的功能。P4/PGR和miRNA可单独在雌性生殖中发挥调控作用。然而,在雌性生殖过程中,miRNA和P4/PGR的相互作用对调控排卵等雌性生殖活动起到非常重要的作用,但作用机制还未阐明。本文综述了miRNA调节P4产生、PGR基因表达以及P4/PGR调节miRNA表达的可能作用方式,为更好地研究miRNA和P4/PGR在雌性生殖中的作用提供理论基础。     

Virus-encoded microRNAs: novel regulators of gene expression

MicroRNAs (miRNAs) are a class of small RNAs that have recently been recognized as major regulators of gene expression. They influence diverse cellular processes ranging from cellular differentiation, proliferation, apoptosis and metabolism to cancer. Bioinformatic approaches and direct cloning methods have identified >3500 miRNAs, including orthologues from various species. Experiments to identify the targets and potential functions of miRNAs in various species are continuing but the recent discovery of virus-encoded miRNAs indicates that viruses also use this fundamental mode of gene regulation. Virus-encoded miRNAs seem to evolve rapidly and regulate both the viral life cycle and the interaction between viruses and their hosts.     

MicroRNA 与垂体腺瘤关系的研究进展

MicroRNA(miRNA)是新发现的一类特殊的小分子RNA,在基因的转录后调控中扮演重要的角色.研究发现很多良恶性肿瘤在发生发展过程中都伴有miRNA的异常表达,所以miRNA的转录后调控机制以及在肿瘤成瘤过程中的作用逐渐成为当下研究的热点,本文就目前垂体腺瘤与miRNA的研究现状做以简要概述.     

MicroRNA functions in insects

MicroRNAs (miRNAs) are small non-coding RNAs that are generated in all eukaryotes and viruses. Their role as master regulators of gene expression in various biological processes has only been fully appreciated over the last decade. Accumulating evidence suggests that alterations in the expression of miRNAs may lead to disorders, including developmental defects, diseases and cancer. Here, I review what is currently known about miRNA functions in insects to provide an insight into their diverse roles in insect biology.     

Small non-coding RNAs in animal development

The modulation of gene expression by small non-coding RNAs is a recently discovered level of gene regulation in animals and plants. In particular, microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs) have been implicated in various aspects of animal development, such as neuronal, muscle and germline development. During the past year, an improved understanding of the biological functions of small non-coding RNAs has been fostered by the analysis of genetic deletions of individual miRNAs in mammals. These studies show that miRNAs are key regulators of animal development and are potential human disease loci.     

MicroRNAs in Drosophila: The magic wand to enter the Chamber of Secrets?

MicroRNAs are small non-coding RNAs that are now recognised as key regulators of gene expression in eukaryotes. Over the past few years, hundreds of miRNAs have been identified from various organisms including vertebrates, nematodes, insects and plants. A high level of conservation of some miRNAs from animals to plants underlines their crucial role in eukaryotes. Although biogenesis and mode of action of miRNAs are now quite well understood, their numerous and specific regulatory functions remain to be unravelled. In this review, we summarise the current knowledge on miRNAs in insects, which was mainly acquired through the study of the fruit fly, Drosophila melanogaster.     

动物中microRNA 的保守性和进化历程

microRNA 是一类长度约为22 个核苷酸的内源性非编码单链RNA, 在后生动物中普遍存在, 在转录后过程调控基因表达. miRNA 在个体发育过程中发挥着各种功能, 如发育时序调控和细胞分化、神经发育等. miRNA 在各种后生动物中具有保守性, 而且多个关键类群的出现皆伴随着大量新miRNA 的产生, 这些现象都表明miRNA 与动物的系统发生密切相关. 本文从miRNA 的产生和作用机制、在后生动物中的分布格局及其在个体发育中的调控功能3 个方面论述了miRNA 的保守性, 并结合miRNA 的发生和发展历程, 探讨了miRNA 在动物进化中起到的重要作用.     

Signature miRNAs involved in the innate immunity of invertebrates

The innate immune system, including the cell-based immunity (mainly apoptosis and phagocytosis) and the humoral immunity (such as pro-phenoloxidase system), is the first defense line of animals against the infection of pathogens in a non-specific manner, which is fine regulated through the gene expression regulations. The microRNAs (miRNAs) are recognized as important regulators of gene expression. To date, however, a comprehensive view about the regulation of innate immunity by miRNAs is not available. To address this issue, the signature miRNAs involved in the innate immunity were characterized in this study. The phagocytosis, apoptosis and phenoloxidase (PO), a key enzyme in the pro-phenoloxidase system, of invertebrate shrimp were activated or inhibited, followed by the small RNA sequencing. The results showed that a total of 24 miRNAs took great effects on phagocytosis, apoptosis or the pro-phenoloxidase system, which were further confirmed by Northern blots. Among the 24 innate immunity-associated miRNAs, 21 miRNAs were conserved in animals, suggesting that these miRNAs might share the similar or the same functions in different species of animals. Based on degradome sequencing and prediction of target genes, it was found that the miRNAs might mediate the regulations of phagocytosis, apoptosis or pro-phenoloxidase system by targeting different genes. Therefore our study presented the first comprehensive view of the miRNAs associated with innate immunity, which would facilitate to reveal the molecular events in the regulation of innate immunity.     

小RNA分子与精子发生调控

近来研究发现小RNA(small RNAs)可作为转录后及翻译水平上基因表达调节的重要调节因子,利用小RNA来阐明调节精子发生的分子机制取得了显著进展。这些小RNA主要分为3类,即小干扰RNA(siRNA)、微小RNA(miRNA)以及与piwi蛋白相互作用的RNA(piRNA)。在减数分裂和精子发生过程中,小RNA具有多种生物学功能,如利用siRNA体外转染或体内注射来敲低特定基因从而研究该基因在精子发生过程中的作用;miRNA可能参与精子发生中有丝、减数及后减数分裂阶段的基因表达调节;piRNA主要参与调节雄性生殖细胞减数及后减数分裂的过程,在精子发生中起抑制反转录转座子(retrotransposons)的作用。文章对小RNAs合成、作用机制、功能及展望等最新进展进行了综述。     

The small RNA expression profile of the developing murine urinary and reproductive systems

microRNAs (miRNAs) are small non-coding RNAs with fundamental roles in the regulation of gene expression. miRNAs assemble with Argonaute (Ago) proteins to miRNA-protein complexes (miRNPs), which interact with distinct binding sites on mRNAs and regulate gene expression. Specific miRNAs are key regulators of tissue and organ development and it has been shown in mammals that miRNAs are also involved in the pathogenesis of many diseases including cancer. Here, we have characterized the miRNA expression profile of the developing murine genitourinary system. Using a computational approach, we have identified several miRNAs that are specific for the analyzed tissues or the developmental stage. Our comprehensive miRNA expression atlas of the developing genitourinary system forms an invaluable basis for further functional in vivo studies.     

MicroRNAs and intestinal pathophysiology

MicroRNAs (miRNAs) represent an abundant class of endogenously expressed small RNAs, which is believed to control the expression of proteins through specific interaction with their mRNAs. MiRNAs are non-coding RNAs of 18 to 24 nucleotides that negatively regulate target mRNAs by binding to their 3'-untranslated regions (UTR). Most eukaryotic cells utilize miRNA to regulate vital functions such as cell differentiation, proliferation or apopotosis. The diversity of miRNAs and of their mRNA targets strongly indicate that they play a key role in the regulation of protein expression. To date, more than 500 different miRNAs have been identified in animals and plants. There are at least 326 miRNAs in the human genome, comprising 1-4% of all expressed human genes, which makes miRNAs one of the largest classes of gene regulators. A single miRNA can bind to and regulate many different mRNA targets and, conversely, several different miRNAs can bind to and cooperatively control a single mRNA target. The correlation between the expression of miRNAs and their effects on tumorigenesis and on the proliferation of cancer cells is beginning to gain experimental evidences. Recent studies showed that abnormal expression of miRNAs represents a common feature of cancer cells and that they can function as tumor suppressor genes or as oncogenes. Therefore, this diversity of action for miRNAs on several target genes could be one of the common mechanisms involved in the deregulation of protein expression observed during intestinal disorders. In this review, the emergent functions of miRNAs in colorectal cancer and their potential role in the intestinal inflammatory process are discussed.     

Identifying MicroRNAs Involved in Degeneration of the Organ of Corti during Age-Related Hearing Loss

MicroRNAs (miRNAs), a class of short non-coding RNAs that regulate the expression of mRNA targets, are important regulators of cellular senescence and aging. We questioned which miRNAs are involved in age-related degeneration of the organ of Corti (OC), the auditory sensory epithelium that transduces mechanical stimuli to electrical activity in the inner ear. Degeneration of the OC is generally accepted as the main cause of age-related hearing loss (ARHL), a progressive loss of hearing in individuals as they grow older. To determine which miRNAs are involved in the onset and progression of ARHL, miRNA gene expression in the OC of two mouse strains, C57BL/6J and CBA/J, was compared at three different ages using GeneChip miRNA microarray and was validated by real-time PCR. We showed that 111 and 71 miRNAs exhibited differential expression in the C57 and CBA mice, respectively, and that downregulated miRNAs substantially outnumbered upregulated miRNAs during aging. miRNAs that had approximately 2-fold upregulation included members of miR-29 family and miR-34 family, which are known regulators of pro-apoptotic pathways. In contrast, miRNAs that were downregulated by about 2-fold were members of the miR-181 family and miR-183 family, which are known to be important for proliferation and differentiation, respectively. The shift of miRNA expression favoring apoptosis occurred earlier than detectable hearing threshold elevation and hair cell loss. Our study suggests that changes in miRNA expression precede morphological and functional changes, and that upregulation of pro-apoptotic miRNAs and downregulation of miRNAs promoting proliferation and differentiation are both involved in age-related degeneration of the OC.