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.     

Computational approaches for microRNA studies: a review

MicroRNAs (miRNAs) are one class of tiny, endogenous RNAs that can regulate messenger RNA (mRNA) expression by targeting homologous sequences in mRNAs. Their aberrant expressions have been observed in many cancers and several miRNAs have been convincingly shown to play important roles in carcinogenesis. Since the discovery of this small regulator, computational methods have been indispensable tools in miRNA gene finding and functional studies. In this review we first briefly outline the biological findings of miRNA genes, such as genomic feature, biogenesis, gene structure, and functional mechanism. We then discuss in detail the three main aspects of miRNA computational studies: miRNA gene finding, miRNA target prediction, and regulation of miRNA genes. Finally, we provide perspectives on some emerging issues, including combinatorial regulation by miRNAs and functional binding sites beyond the 3′-untranslated region (3′UTR) of target mRNAs. Available online resources for miRNA computational studies are also provided.     

Highly specific gene silencing by artificial microRNAs in the unicellular alga Chlamydomonas reinhardtii

MicroRNAs (miRNAs) are small RNAs, 21 to 22 nucleotides long, with important regulatory roles. They are processed from longer RNA molecules with imperfectly matched foldback regions and they function in modulating the stability and translation of mRNA. Recently, we and others have demonstrated that the unicellular alga Chlamydomonas reinhardtii , like diverse multicellular organisms, contains miRNAs. These RNAs resemble the miRNAs of land plants in that they direct site-specific cleavage of target mRNA with miRNA-complementary motifs and, presumably, act as regulatory molecules in growth and development. Utilizing these findings we have developed a novel artificial miRNA system based on ligation of DNA oligonucleotides that can be used for specific high-throughput gene silencing in green algae.     

微RNA调节肺癌转移的分子机制

微RNA(microRNA,miRNA)是一类长约22 nt的非编码小分子RNA,在转录后水平上通过基因沉默调节靶基因的活性。近年来,miRNA与肿瘤转移关系的研究成为探讨肿瘤转移调控机制的热点。越来越多的研究提示miRNA在肿瘤转移过程中发挥着重要作用。肺癌转移是影响肺癌预后的关键,是一种复杂的多因素、多步骤、多基因参与调控的过程。研究miRNA对肺癌转移的作用有助于我们找到阻断肺癌转移的靶点。本文就miRNA和肺癌转移关系的研究进展作一综述。     

miRNAs的表达调控机制

microRNAs(miRNAs)是一类在转录后基因调控中发挥功能的非编码小RNAs,在发育、生长和分化等过程中发挥重要作用.至今已经在动物、植物和微生物等不同生物体中鉴定出来数千种miRNAs. miRNAs可以通过降解mRNA或抑制蛋白翻译的方式调节特异基因表达.生物体内约30%的基因都受miRNAs的调节.miRNAs的表达与功能受到转录因子、表观遗传学、多核苷酸多态性及其RNA编辑等多种因素的调节.此外,特异miRNA基因敲除的成功为研究miRNAs功能提供了有力的实验模型.     

A genome-wide survey of microRNA truncation and 3′ nucleotide addition events in larch (Larix leptolepis)

MicroRNAs (miRNAs) play essential roles in numerous developmental and metabolic processes in animals and plants. Although the framework of miRNA biogenesis and function is established, the mechanism of miRNA degradation or modification remains to be investigated in plants. Mature miRNAs may be truncated or added nucleotides to generate variants. A detailed analysis of small RNA deep sequencing data sets resulted in the cloning of a large number of variants derived from larch miRNAs. Many 5′- and/or 3′-end truncated versions of miRNAs suggested that larch miRNAs might be degraded through either 5′–3′ or 3′–5′. The relative abundance of variants truncated from 3′-end was higher than that of 5′-end for most miRNAs. The addition of adenine, uridine, and cytidine to the 3′-end of miRNAs was globally present, and the subtle variability in isomiR abundance might be regulated and biologically meaningful. It is the first report for cytidine addition in plant, and our examination of published small RNA deep sequencing data sets of Arabidopsis, rice, and moss suggests that cytidine addition to miRNA 3′-end exists broadly in plants. In addition, the nucleotide addition might be associated with 3′–5′ miRNA degradation. Our results provide valuable information for a genome-wide survey of miRNA truncation and modification in larch or plants.     

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.     

Identification and Characteristics of Cattle MicroRNAs by Homology Searching and Small RNA Cloning

MicroRNAs (miRNA) are a class of noncoding RNA molecules that regulate gene expression by an RNA-interfering pathway through cleavage or inhibition of the translation of target mRNA. The 254 cattle miRNA candidates found by homology searching frequently clustered at certain chromosomes, and some are possibly expressed from more than one genomic locus. They were partially verified by cloning from a small cattle RNA library, where 31 distinct miRNAs were identified: 18 previously registered in the database of miRBase, 11 novel and homologous to known mammalian miRNAs, and 2 potentially novel without homology to any known miRNAs. Partial miRNA expression was detected by RT-PCR in cattle tissues, such as brain, liver, lung, and heart; some were expressed in all tissues and others in a specific tissue. Sequence alignments revealed that many had end variants, most of which differed in the 3′ end; a small number differed in the 5′ end. This indicates that the same miRNA gene can be individually modified in the process of miRNA biogenesis and could have a different role in regulating target gene expression.     

MicroRNA调控的分子影像研究进展

MicroRNAs(miRNAs)是一类长度约为22个核苷酸的RNA分子,它们通过与靶标mRNAs完全或不完全互补配对,进而导致靶标mRNA的降解或翻译的抑制.大量研究表明,它们在细胞增殖、分化、凋亡和肿瘤形成等广泛的生物学过程中都起着重要的作用.传统检测miRNAs表达的方法主要包括Northern杂交、实时定量PC...