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.     

The discovery approaches and detection methods of microRNAs

MicroRNAs (miRNAs) are small, highly conserved, non-coding RNAs that regulate gene expression of target mRNAs through cleavage or translational inhibition. Computer-based approaches for miRNA gene identification are being considered as indispensable in miRNAs research. Similarly, experimental approaches for detection of miRNAs are crucial to the testing and validating of computational algorithms. The detection of miRNAs in tissues or cells can supply valuable information for investigating the biological function of these molecules. Selective and highly sensitive detection methods will pave the way for extended understanding of miRNA function within organisms. In this review, we summarize the various computational methods for identification of miRNAs as well as the methodologies that have been developed to detection miRNAs.     

microPrimer: the biogenesis and function of microRNA

Discovered in nematodes in 1993, microRNAs (miRNAs) are non-coding RNAs that are related to small interfering RNAs (siRNAs), the small RNAs that guide RNA interference (RNAi). miRNAs sculpt gene expression profiles during plant and animal development. In fact, miRNAs may regulate as many as one-third of human genes. miRNAs are found only in plants and animals, and in the viruses that infect them. miRNAs function very much like siRNAs, but these two types of small RNAs can be distinguished by their distinct pathways for maturation and by the logic by which they regulate gene expression.     

Mobile microRNAs hit the target

MicroRNAs (miRNAs) are negative regulators of gene expression in eukaryotic organisms, whereas small interfering RNAs (siRNAs) guide host-cell defence against viruses, transposons and transgenes. A key issue in plant biology is whether miRNAs act only in cells in which they are formed, or if, like siRNAs, they also function after passive diffusion or active transportation into other cells. Recent reports show that miRNAs are indeed able to move between plant cells to direct developmental programming of gene expression. In both leaf and root development, miRNAs establish intercellular gradients of gene expression that are essential for cell and tissue differentiation. Gradients in gene expression also play crucial roles in animal development, and there is strong evidence for intercellular movement of miRNAs in animals. Thus, intercellular movement of miRNAs may be crucial to animal developmental biology as well as plants.     

Isolation and identification of novel microRNAs from Marsupenaeus japonicus

MicroRNAs (miRNAs) are a class of small noncoding RNAs that function as regulators of gene expression. They play essential roles in various biological processes, such as development, differentiation and immune response. In this study, we identified 35 miRNAs from Marsupenaeus japonicus. Among them, fifteen miRNAs exhibited high homology to the known miRNAs from other arthropods, while the rest might represent novel miRNAs. We further showed a correlation of WSSV infection and the expression levels of 22 miRNAs. This is the first report to identify miRNAs from the shrimp. Our results extend the knowledge of the gene regulation of crustacean, providing clues for future researches of shrimp immunity against virus infection.     

The evolution of animal microRNA function

MicroRNAs (miRNAs) are a large class of small RNAs that function as negative gene regulators in eukaryotes. They regulate diverse biological processes, and bioinformatics data indicate that each miRNA can control hundreds of gene targets, underscoring the potential influence of miRNAs on almost every genetic pathway. In addition to the roles in ontogeny, recent evidence has suggested the possibility that miRNAs have huge impacts on animal phylogeny. The dramatically expanding repertoire of miRNAs and their targets appears to be associated with major body-plan innovations as well as the emergence of phenotypic variation in closely related species. Research in the area of miRNA phylogenetic conservation and diversity suggests that miRNAs play important roles in animal evolution, by driving phenotypic variation during development.     

Systematic investigation of Amphioxus (Branchiostoma floridae) microRNAs

MicroRNAs (miRNAs) participate in various biological processes via controlling gene activity. Amphioxus is the best available stand-in as the proximate invertebrate ancestor of the vertebrates. Here, we systematically investigated the miRNAs in amphioxus. First, we identified 245 candidate amphioxus miRNAs, in which 183 miRNAs were firstly reported. Second, we gave evidences to support a birth-and-death process of miRNA genes in some families and gave implications for the functional diversification of miRNA during evolution. Third, we identified 47 development-specific expression miRNAs. We found that only 19 miRNAs were expressed in all developmental stages, 16 miRNAs were neurula-specific and 13 miRNAs were larva-specific. In addition, these potential miRNA-targeting genes were mainly classified into development, muscle formation, cell adhesion, and gene regulation categories. Finally, we found 79 immune related genes targeted by 136 miRNAs in amphioxus. In conclusion, our results take an insight into both the function and evolution of the amphioxus miRNAs.     

小RNA(MicroRNA)研究方法

小RNA (microRNA)是一类新发现的长度约为21～25个核苷酸的RNA,它在转录后水平调节靶基因表达.已有研究表明,小RNA在发育、细胞增殖、凋亡、脂类代谢、激素分泌及肿瘤发生等多种生理和病理过程中发挥重要作用.针对小RNA的研究方法主要包括两大类:一是以传统实验技术方法为基础建立起来的小RNA特有的技术方法,二是已成熟应用的生物信息学技术.前者侧重于小RNA表达的检测和功能机制的阐明,后者则包括新小RNA基因及小RNA靶基因的预测.两者相辅相成,互为补充,为深入地研究这类分子的功能和分子机制提供了大量功能线索,及确凿的实验证据.     

MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship

MicroRNAs (miRNAs) have emerged as key gene regulators in diverse biological pathways. These small non-coding RNAs bind to target sequences in mRNAs, typically resulting in repressed gene expression. Several methods are now available for identifying miRNA target sites, but the mere presence of an miRNA-binding site is insufficient for predicting target regulation. Regulation of targets by miRNAs is subject to various levels of control, and recent developments have presented a new twist; targets can reciprocally control the level and function of miRNAs. This mutual regulation of miRNAs and target genes is challenging our understanding of the gene-regulatory role of miRNAs in vivo and has important implications for the use of these RNAs in therapeutic settings.     

Instability of miRNA and cDNAs derivatives in RNA preparations

Micro RNAs (miRNAs) are small RNA molecules, which function as important regulators of gene expression. We found that RNA preparation methods commonly utilized for miRNA expression studies yield highly unstable miRNAs. We studied the stability of four miRNAs belonging to different miRNAs families. A significant degradation of these molecules may be observed already three days after RNA isolation. Moreover, the respective cDNAs are highly unstable as well. Our findings indicate that instability of miRNAs and their cDNAs should be considered when designing miRNA expression studies.     

microRNAs: small molecules with big roles - C. elegans to human cancer

miRNAs (microRNAs) were first discovered as critical regulators of developmental timing events in Caenorhabditis elegans. Subsequent studies have shown that miRNAs and cellular factors necessary for miRNA biogenesis are conserved in many organisms, suggesting the importance of miRNAs during developmental processes. Indeed, mutations in the miRNA-processing pathway induce pleiotropic defects in development, which accompany perturbation of correct expression of target genes. However, control of gene expression in development is not the only function of miRNAs. Recent work has provided new insights into the role of miRNAs in various biological events, including aging and cancer. C. elegans continues to be helpful in facilitating a further understanding of miRNA function in human diseases.