Long noncoding RNA complementarity and target transcripts abundance

Eukaryotic mRNA metabolism regulates its stability, localization, and translation using complementarity with counter-part RNAs. To modulate their stability, small and long noncoding RNAs can establish complementarity with their target mRNAs. Although complementarity of small interfering RNAs and microRNAs with target mRNAs has been studied thoroughly, partial complementarity of long noncoding RNAs (lncRNAs) with their target mRNAs has not been investigated clearly. To address that research gap, our lab investigated whether the sequence complementarity of two lncRNAs, lincRNA-p21 and OIP5-AS1, influenced the quantity of target RNA expression. We predicted a positive correlation between lncRNA complementarity and target mRNA quantity. We confirmed this prediction using RNA affinity pull down, microarray, and RNA-sequencing analysis. In addition, we utilized the information from this analysis to compare the quantity of target mRNAs when two lncRNAs, lincRNA-p21 and OIP5-AS1, are depleted by siRNAs. We observed that human and mouse lincRNA-p21 regulated target mRNA abundance in complementarity-dependent and independent manners. In contrast, affinity pull down of OIP5-AS1 revealed that changes in OIP5-AS1 expression influenced the amount of some OIP5-AS1 target mRNAs and miRNAs, as we predicted from our sequence complementarity assay. Altogether, the current study demonstrates that partial complementarity of lncRNAs and mRNAs (even miRNAs) assist in determining target RNA expression and quantity.     

Global analysis of microRNA target gene expression reveals the potential roles of microRNAs in maintaining tissue identity

Background  

MicroRNAs are non-coding small RNAs of ~22 nucleotides that regulate the gene expression by base-paring with target mRNAs, leading to mRNA cleavage or translational repression. It is currently estimated that microRNAs account for ~ 1% of predicted genes in higher eukaryotic genomes and that up to 30% of genes might be regulated by microRNAs. However, only very few microRNAs have been functionally characterized and the general functions of microRNAs are not globally studied.     

Gene regulation by non-coding RNAs

Abstract

The past two decades have seen an explosion in research on non-coding RNAs and their physiological and pathological functions. Several classes of small (20–30 nucleotides) and long (>200 nucleotides) non-coding RNAs have been firmly established as key regulators of gene expression in myriad processes ranging from embryonic development to innate immunity. In this review, we focus on our current understanding of the molecular mechanisms underlying the biogenesis and function of small interfering RNAs (siRNAs), microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs). In addition, we briefly review the relevance of small and long non-coding RNAs to human physiology and pathology and their potential to be exploited as therapeutic agents.     

Sly-miR166 and Sly-miR319 are components of the cold stress response in Solanum lycopersicum

MicroRNAs (miRNAs) are a class of small endogenous non-coding RNAs that modulate gene expression in both plants and animals and are involved in several biological processes, ranging from organ differentiation to biotic and abiotic stress responses. We identified two cold stress response microRNAs that showed differential expression in Solanum lycopersicum plants subjected to cold stress. We observed that Sly-miR166 and Sly-miR319 were up-regulated by cold treatments. The up-regulation of Sly-miR166 and Sly-miR319 in cold stress-treated S. lycopersicum seedlings and the down-regulation of their respective targets, HD-Zip III and GAMyb-like that validate by 5′-RACE technique, suggests that these miRNAs play a critical role in regulating S. lycopersicum responses to cold stress.     

Expression of miRNAs in ovine fetal gonads: potential role in gonadal differentiation

Background  

Gonadal differentiation in the mammalian fetus involves a complex dose-dependent genetic network. Initiation and progression of fetal ovarian and testicular pathways are accompanied by dynamic expression patterns of thousands of genes. We postulate these expression patterns are regulated by small non-coding RNAs called microRNAs (miRNAs). The aim of this study was to identify the expression of miRNAs in mammalian fetal gonads using sheep as a model.     

Reconstructing the coding and non-coding RNA regulatory networks of miRNAs and mRNAs in breast cancer

microRNAs (miRNAs) are a class of small non-coding RNAs that deregulate and/or decrease the expression of target messenger RNAs (mRNAs), which specifically contribute to complex diseases. In our study, we reanalyzed an integrated data to promote classification performance by rebuilding miRNA–mRNA modules, in which a group of deregulated miRNAs cooperatively regulated a group of significant mRNAs. In five-fold cross validation, the multiple processes flow considered the biological and statistical significant correlations. First, of statistical significant miRNAs, 6 were identified as core miRNAs. Second, in the 13 significant pathways enriched by gene set enrichment analysis (GSEA), 705 deregulated mRNAs were found. Based on the union of predicted sets and correlation sets, 6 modules were built. Finally, after verified by test sets, three indexes, including area under the ROC curve (AUC), Accuracy and Matthews correlation coefficients (MCCs), indicated only 4 modules (miR-106b-CIT-KPNA2-miR-93, miR-106b-POLQ-miR-93, miR-107-BTRC-UBR3-miR-16 and miR-200c-miR-16-EIF2B5-miR-15b) had discriminated ability and their classification performance were prior to that of the single molecules. By applying this flow to different subtypes, Module 1 was the consistent module across subtypes, but some different modules were still specific to each subtype. Taken together, this method gives new insight to building modules related to complex diseases and simultaneously can give a supplement to explain the mechanism of breast cancer (BC).     

植物小RNAs及其抗胁迫机制研究进展

植物非编码小RNA(sRNAs)主要分为三类:微小RNA(m iRNAs)、小干扰RNA(siRNAs)和长小片段干扰RNA(lsiRNAs)。三者的生物合成和作用机制有所不同,但他们主要都通过介导靶mRNAs的剪切或抑制其翻译来调控基因的表达。这篇文章主要介绍小RNA研究的最新进展,并重点阐述其在非生物和生物胁迫中发挥的作用,如应对矿质元素缺乏、氧化胁迫、ABA胁迫以及病原菌入侵等生理过程。     

MicroRNA 128a Increases Intracellular ROS Level by Targeting Bmi-1 and Inhibits Medulloblastoma Cancer Cell Growth by Promoting Senescence

Background

MicroRNAs (miRNAs) are a class of short non-coding RNAs that regulate cell homeostasis by inhibiting translation or degrading mRNA of target genes, and thereby can act as tumor suppressor genes or oncogenes. The role of microRNAs in medulloblastoma has only recently been addressed. We hypothesized that microRNAs differentially expressed during normal CNS development might be abnormally regulated in medulloblastoma and are functionally important for medulloblastoma cell growth.

Methodology and Principal Findings

We examined the expression of microRNAs in medulloblastoma and then investigated the functional role of one specific one, miR-128a, in regulating medulloblastoma cell growth. We found that many microRNAs associated with normal neuronal differentiation are significantly down regulated in medulloblastoma. One of these, miR-128a, inhibits growth of medulloblastoma cells by targeting the Bmi-1 oncogene. In addition, miR-128a alters the intracellular redox state of the tumor cells and promotes cellular senescence.

Conclusions and Significance

Here we report the novel regulation of reactive oxygen species (ROS) by microRNA 128a via the specific inhibition of the Bmi-1 oncogene. We demonstrate that miR-128a has growth suppressive activity in medulloblastoma and that this activity is partially mediated by targeting Bmi-1. This data has implications for the modulation of redox states in cancer stem cells, which are thought to be resistant to therapy due to their low ROS states.     

Microarray profiling of monocytic differentiation reveals miRNA-mRNA intrinsic correlation

MiRNAs (microRNAs) are small non-coding RNAs involved in mammalian gene expression of cellular processes including differentiation, apoptosis and cancer development. Both specific miRNAs and mRNAs have been identified during monocytic differentiation, but their interactions have not been fully characterized. Here we report that by genome-wide microarray analysis for U937 monocytic differentiation induced by TPA, a large number of miRNAs and mRNAs were differentially expressed, and by bioinformatics analysis could demonstrate that their functional pathway patterns overlap strongly. While expected negative correlation between the expression levels of miRNAs and their target mRNAs was seen, several positive correlations between miRNAs and host mRNAs were also observed, such as C13orf25/miR17, MCM7/miR93, and MGC14376/miR22. These microarray data were verified by quantitative RT-PCR, and the TPA-induced differentiation of U937 cells was confirmed by flow cytometric analysis. Our study suggests an intrinsic correlation between miRNAs and mRNAs underlying their interactions which would provide new insights for defining the mechanisms occurring during monocytic differentiation.     

The miR200 Family of MicroRNAs Regulates WAVE3-dependent Cancer Cell Invasion

MicroRNAs are small non-coding RNAs that are directly involved in the regulation of gene expression by either translational repression or degradation of target mRNAs. Because of the high level of conservation of the target motifs, known as seed sequences, within the 3′-untranslated regions, a single microRNA can regulate numerous target genes simultaneously, making this class of RNAs a powerful regulator of gene expression. The miR200 family of microRNAs has recently been shown to regulate the process of epithelial to mesenchymal transition during tumor progression and metastasis. Here, we report that the expression of WAVE3, an actin cytoskeleton remodeling and metastasis promoter protein, is regulated by miR200 microRNAs. We show a clear inverse correlation between expression levels of WAVE3 and miR200 microRNAs in invasive versus non-invasive cancer cells. miR200 directly targets the 3′-untranslated regions of the WAVE3 mRNA and inhibits its expression. The miR200-mediated down-regulation of WAVE3 results in a significant reduction in the invasive phenotype of cancer cells, which is specific to the loss of WAVE3 expression. Re-expression of a miR200-resistant WAVE3 reverses miR200-mediated inhibition of cancer cell invasion. Loss of WAVE3 expression downstream of miR200 also results in a dramatic change in cell morphology resembling that of a mesenchymal to epithelial transition. In conclusion, a novel mechanism for the regulation of WAVE3 expression in cancer cells has been identified, which controls the invasive properties and morphology of cancer cells associated with their metastatic potential.