The Characterization of microRNA-Mediated Gene Regulation as Impacted by Both Target Site Location and Seed Match Type

MicroRNAs (miRNAs) are small RNA molecules that play important roles in gene regulation and translational repression. The mechanisms that facilitate miRNA target binding and recognition have been extensively studied in recent years. However, it is still not well known how the miRNA regulation is affected by the location and the flanking sequences of miRNA target sites. In this study, we systematically quantify the contribution of a wide spectrum of target sites on miRNA-mediated gene expression regulation. Our study investigates target sites located in four different gene regions, including 3'' untranslated regions, coding sequences, 5′ untranslated regions and promoter regions. We have also introduced four additional non-canonical types of seed matches beyond the canonical seed matches, and included them in our study. Computational analysis of quantitative proteomic data has demonstrated that target sites located in different regions impact the miRNA-mediated repression differently but synergistically. In addition, we have shown the synergistic effects among non-canonical seed matches and canonical ones that enhance the miRNA regulatory effects. Further systematic analysis on the site accessibility near the target regions and the secondary structure of the mRNA sequences have demonstrated substantial variations among target sites of different locations and of different types of seed matches, suggesting the mRNA secondary structure could explain some of the difference in the miRNA regulatory effects impacted by these different target sites. Our study implies miRNAs might regulate their targets under different mechanisms when target sites vary in both their locations and the types of seed matches they contain.     

Profiling of regulatory microRNA transcriptomes in various biological processes: a review

A class of small, non-coding ribonucleic acids, termed microRNA (miRNA), has recently emerged as a new key player in the cellular control of gene expression. By either blocking translation or inducing target mRNA degradation, miRNA not only participates in regular biological processes within cells and tissues but is also involved in pathological processes. Many human malignancies have been linked to specific miRNA expression patterns, raising hopes for new approaches to therapy. While such human disease-related mechanisms have been widely discussed and frequently reviewed, miRNA’s general significance in animals has been less in editorial focus, despite its obvious role in basic physiological processes, e.g. neurosensory maturation, development of fertility, and hibernation. Using selected examples, this review highlights our current knowledge of miRNA’s potential and its promise as a new tool for gene regulation.     

miSSING LINKS: miRNAs and plant development

The discovery of hundreds of plant micro RNAs (miRNAs) has triggered much speculation about their potential roles in plant development. The search for plant genes involved in miRNA processing has revealed common factors such as DICER, and new molecules, including HEN1. Progress is also being made toward identifying miRNA target genes and understanding the mechanisms of miRNA-mediated gene regulation in plants. This work has lead to a reexamination of many previously characterized mutations that are now known to affect components or targets of miRNA-mediated pathways.     

miRNA，siRNA，saRNA与基因表达调控

近年来的研究发现,生物体内存在着大量的非编码RNA（non．codingRNAs,ncRNA）,它们在染色质修饰、基因转录、RNA剪接和mRNA翻译等多种水平上参与了基因表达的调控。ncRNA中的小分子RNA如miRNA能够识别特定的目标mRNA,通过与mRNAs3’非翻译区结合,影响mRNA转录及蛋白质翻译;siRNA是RNA干扰的引发物,能够导致与dsRNA同源的mRNA降解,进而抑制相应基因表达;saRNA是目前最新发现的一种靶向目的基因启动子区的在转录水平激活目的基因表达的dsRNA。miRNA、siRNA和saRNA在生成机制、作用途径等方面关系密切,既区别又相互联系,小分子RNA的研究将是今后分子生物学的研究热点之一。     

Polypyrimidine tract binding protein (hnRNP I) is possibly a conserved modulator of miRNA-mediated gene regulation

MiRNAs can regulate gene expression through versatile mechanisms that result in increased or decreased expression of the targeted mRNA and it could effect the expression of thousands of protein in a particular cell. An increasing body of evidence suggest that miRNAs action can be modulated by proteins that bind to the same 3'UTRs that are targeted by miRNAs, suggesting that other factors apart from miRNAs and their target sites determine miRNA-modulation of gene expression. We applied an affinity purification protocol using biotinylated let-7 miRNA inhibitor to isolate proteins that are involved in let-7 mediated gene regulation that resulted in an affinity purification of Polypyrimidine Tract Binding protein (PTB). Here we show that PTB interacts with miRNAs and human Argonaute 2 (hAgo2) through RNA as well as identified potential mammalian cellular targets that are co-regulated by PTB and hAgo2. In addition, using genetic approach, we have demonstrated that PTB genetically interacts with Caenorhabditis elegans let-7 indicating a conserved role for PTB in miRNA-mediated gene regulation.     

Mechanisms of microRNA-mediated gene regulation

microRNAs (miRNAs) are identified as a class of non-protein regulators and a new source for broad control of gene expression in eukaryotes. The past years have witnessed substantial progress in understanding miRNA functions and mechanisms, although a few controversies remain. Various hypotheses and models have been suggested for the mechanisms of miRNA repression, including translational inhibition at the level of initiation or elongation, rapid degradation of the nascent peptide, mRNA degradation, and mRNA sequestration into P bodies (processing bodies) and SGs (stress granules) for degradation or/and storage. Recently, some noncanonical miRNA regulation, such as miRNA activation and de-repression of miRNA inhibition, have been uncovered. This review discusses some recent advances about how miRNAs regulate their targets and various modes of miRNA function.     

Critical Roles of microRNAs in the Pathogenesis of Fatty Liver: New Advances,Challenges, and Potential Directions

In this review, we summarize the current understanding of microRNA (miRNA)-mediated modulation of the gene expression in the fatty liver as well as related signaling pathways. Because of the breadth and diversity of miRNAs, miRNAs may have a very wide variety of biological functions, and much evidence has confirmed that miRNAs are involved in the pathogenesis of fatty liver. In the pathophysiological mechanism of fatty liver, miRNAs may be regulated by upstream regulators, and have their own regulatory targets. miRNAs display important roles in the pathological mechanisms of alcoholic liver disease and non-alcoholic fatty liver disease. At present, most of the miRNA studies are focused on cell and tissue levels, and in vivo studies will help us elucidate the regulation of miRNAs and help us evaluate the potential of miRNAs as diagnostic markers and therapeutic targets. Furthermore, there is evidence that miRNAs are involved in the mechanism of natural medicine treatment in fatty liver. Given the important roles of miRNAs in the pathogenesis of fatty liver, we predict that studies of miRNAs in the pathogenesis of fatty liver will contribute to the elucidation of fatty liver pathology and the treatment of fatty liver patients.