scholarly journals Comprehensive analysis of human microRNA-mRNA interactome

2019 ◽  
Author(s):  
Olga Plotnikova ◽  
Ancha Baranova ◽  
Mikhail Skoblov

AbstractMicroRNAs play a key role in the regulation of gene expression. A majority of microRNA-mRNA interactions remain unidentified. Despite extensive research, our ability to predict human microRNA-mRNA interactions using computational algorithms remains limited by a complexity of the models for non-canonical interactions, and an abundance of false positive results.Here we present the landscape of microRNA-mRNA human interactions, which we derived from comprehensive analysis of datasets describing direct microRNA-mRNA interactions experimentally defined in HEK293 and Huh7.5 cell lines, along with other available microRNA and mRNA expression data. We have also established a collection of reliable microRNA binding regions that we systematically extracted in course of analysis of 79 CLIP datasets, which is available at http://score.generesearch.ru/services/mirna/.While only 1-2% of human genes interact with microRNAs, some RNAs display a substantial sponge effect, which is specific to the cell line of study. Some microRNAs are expressed at a very high level, while interacting with only a few mRNAs, thus, indeed, serving as specific gene expression regulators. Other miRNAs might be expressed at relatively low levels, and interact with many mRNAs. Some of the microRNAs might switch between these two classes, depending on cellular context. Results of our study provide an initial resolution into the complex patterns of human microRNA-mRNA interactions.

Genetics ◽  
1984 ◽  
Vol 108 (3) ◽  
pp. 651-667
Author(s):  
Douglas P Dickinson ◽  
Kenneth W Gross ◽  
Nina Piccini ◽  
Carol M Wilson

ABSTRACT Inbred strains of mice carry Ren-1, a gene encoding the thermostable Renin-1 isozyme. Ren-1 is expressed at relatively low levels in mouse submandibular gland and kidney. Some strains also carry Ren-2, a gene encoding the thermolabile Renin-2 isozyme. Ren-2 is expressed at high levels in the mouse submandibular gland and at very low levels, if at all, in the kidney. Ren-1 and Ren-2 are closely linked on mouse chromosome 1, show extensive homology in coding and noncoding regions and provide a model for studying the regulation of gene expression. An investigation of renin genes and enzymatic activity in wild-derived mice identified several restriction site polymorphisms as well as putative variants in renin gene expression and protein structure. The number of renin genes carried by different subpopulations of wild-derived mice is consistent with the occurrence of a gene duplication event prior to the divergence of M. spretus (2.75-5.5 million yr ago). This conclusion is in agreement with a prior estimate based upon comparative sequence analysis of Ren-1 and Ren-2 from inbred laboratory mice.


Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2152
Author(s):  
Robin Loesch ◽  
Linda Chenane ◽  
Sabine Colnot

Chromatin remodelers are found highly mutated in cancer including hepatocellular carcinoma. These mutations frequently occur in ARID (AT-rich Interactive Domain) genes, encoding subunits of the ATP-dependent SWI/SNF remodelers. The increasingly prevalent complexity that surrounds the functions and specificities of the highly modular BAF (BG1/BRM-associated factors) and PBAF (polybromo-associated BAF) complexes, including ARID1A/B or ARID2, is baffling. The involvement of the SWI/SNF complexes in diverse tissues and processes, and especially in the regulation of gene expression, multiplies the specific outcomes of specific gene alterations. A better understanding of the molecular consequences of specific mutations impairing chromatin remodelers is needed. In this review, we summarize what we know about the tumor-modulating properties of ARID2 in hepatocellular carcinoma.


2015 ◽  
Vol 2015 ◽  
pp. 1-20 ◽  
Author(s):  
Hiroshi Kondo ◽  
Keiko Miyoshi ◽  
Shoji Sakiyama ◽  
Akira Tangoku ◽  
Takafumi Noma

Stem cell therapy appears to be promising for restoring damaged or irreparable lung tissue. However, establishing a simple and reproducible protocol for preparing lung progenitor populations is difficult because the molecular basis for alveolar epithelial cell differentiation is not fully understood. We investigated anin vitrosystem to analyze the regulatory mechanisms of alveolus-specific gene expression using a human alveolar epithelial type II (ATII) cell line, A549. After cloning A549 subpopulations, each clone was classified into five groups according to cell morphology and marker gene expression. Two clones (B7 and H12) were further analyzed. Under serum-free culture conditions,surfactant protein C(SPC), an ATII marker, was upregulated in both H12 and B7.Aquaporin 5(AQP5), an ATI marker, was upregulated in H12 and significantly induced in B7. When the RAS/MAPK pathway was inhibited,SPCandthyroid transcription factor-1(TTF-1) expression levels were enhanced. After treatment with dexamethasone (DEX), 8-bromoadenosine 3′5′-cyclic monophosphate (8-Br-cAMP), 3-isobutyl-1-methylxanthine (IBMX), and keratinocyte growth factor (KGF),surfactant protein BandTTF-1expression levels were enhanced. We found that A549-derived clones have plasticity in gene expression of alveolar epithelial differentiation markers and could be useful in studying ATII maintenance and differentiation.


2021 ◽  
Author(s):  
Qiqi Chen ◽  
Pan Shen ◽  
Ralph Bock ◽  
Shengchun Li ◽  
Jiang Zhang

Abstract A serious limitation in the application of plastid biotechnology is the low-level expression of transgene in non-green plastids like chromoplasts compared with photosynthetically active chloroplasts. Unlike other fruits, not all chloroplasts are transformed into chromoplast during ripening of red-fleshed kiwifruit ( Actinidia chinensis vs Hongyang) fruits, which may make kiwifruit as an ideal horticultural plant for oral vaccine production by plastid engineering. To identify cis -elements potentially triggering high-level transgene expression in edible tissues of the ‘Hongyang’ kiwifruit, here we report a comprehensive analysis of kiwifruit plastid gene transcription in the green leaves and fruits at three different developing stages. While transcripts of a few photosynthesis-related genes and most genetic system genes were substantially upregulated in green fruits compared with leaves, nearly all plastid genes were significantly downregulated at the RNA level during fruit development. Expression of a few genes remained unchanged, including psbA , the gene encoding the D1 polypeptide of photosystem II. However, PsbA protein accumulation decreased continuously during chloroplast-to-chromoplast differentiation. Analysis of post-transcriptional steps in mRNA maturation, including intron splicing and RNA editing, revealed that splicing and editing may contribute to regulating plastid gene expression. Altogether, 40 RNA editing sites were verified, and five of them were newly discovered. Taken together, this study has generated a valuable resource for the analysis of plastid gene expression, and provides cis -elements for future efforts to engineer the plastid genome of kiwifruit.


2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Ana J. Chucair-Elliott ◽  
Sarah R. Ocañas ◽  
David R. Stanford ◽  
Victor A. Ansere ◽  
Kyla B. Buettner ◽  
...  

AbstractEpigenetic regulation of gene expression occurs in a cell type-specific manner. Current cell-type specific neuroepigenetic studies rely on cell sorting methods that can alter cell phenotype and introduce potential confounds. Here we demonstrate and validate a Nuclear Tagging and Translating Ribosome Affinity Purification (NuTRAP) approach for temporally controlled labeling and isolation of ribosomes and nuclei, and thus RNA and DNA, from specific central nervous system cell types. Analysis of gene expression and DNA modifications in astrocytes or microglia from the same animal demonstrates differential usage of DNA methylation and hydroxymethylation in CpG and non-CpG contexts that corresponds to cell type-specific gene expression. Application of this approach in LPS treated mice uncovers microglia-specific transcriptome and epigenome changes in inflammatory pathways that cannot be detected with tissue-level analysis. The NuTRAP model and the validation approaches presented can be applied to any brain cell type for which a cell type-specific cre is available.


Blood ◽  
2019 ◽  
Vol 134 (24) ◽  
pp. 2195-2208 ◽  
Author(s):  
Daniel Sasca ◽  
Haiyang Yun ◽  
George Giotopoulos ◽  
Jakub Szybinski ◽  
Theo Evan ◽  
...  

Cohesin mutations are common in myeloid malignancy. Sasca et al elucidate the potential role of cohesin loss in myelodysplastic syndrome and acute myeloid leukemia (MDS/AML). They demonstrate that cohesin binding is critical for erythroid-specific gene expression and that reduction in cohesin impairs terminal erythroid maturation and promotes myeloid malignancy.


2020 ◽  
Vol 38 (1) ◽  
pp. 397-419
Author(s):  
Michael J. Shapiro ◽  
Virginia Smith Shapiro

T cell development involves stepwise progression through defined stages that give rise to multiple T cell subtypes, and this is accompanied by the establishment of stage-specific gene expression. Changes in chromatin accessibility and chromatin modifications accompany changes in gene expression during T cell development. Chromatin-modifying enzymes that add or reverse covalent modifications to DNA and histones have a critical role in the dynamic regulation of gene expression throughout T cell development. As each chromatin-modifying enzyme has multiple family members that are typically all coexpressed during T cell development, their function is sometimes revealed only when two related enzymes are concurrently deleted. This work has also revealed that the biological effects of these enzymes often involve regulation of a limited set of targets. The growing diversity in the types and sites of modification, as well as the potential for a single enzyme to catalyze multiple modifications, is also highlighted.


PLoS Genetics ◽  
2021 ◽  
Vol 17 (9) ◽  
pp. e1009801
Author(s):  
Karl M. Glastad ◽  
Linyang Ju ◽  
Shelley L. Berger

A key question in the rising field of neuroepigenetics is how behavioral plasticity is established and maintained in the developing CNS of multicellular organisms. Behavior is controlled through systemic changes in hormonal signaling, cell-specific regulation of gene expression, and changes in neuronal connections in the nervous system, however the link between these pathways is unclear. In the ant Camponotus floridanus, the epigenetic corepressor CoREST is a central player in experimentally-induced reprogramming of caste-specific behavior, from soldier (Major worker) to forager (Minor worker). Here, we show this pathway is engaged naturally on a large genomic scale during late pupal development targeting multiple genes differentially expressed between castes, and central to this mechanism is the protein tramtrack (ttk), a DNA binding partner of CoREST. Caste-specific differences in DNA binding of ttk co-binding with CoREST correlate with caste-biased gene expression both in the late pupal stage and immediately after eclosion. However, we find a unique set of exclusive Minor-bound genes that show ttk pre-binding in the late pupal stage preceding CoREST binding, followed by caste-specific gene repression on the first day of eclosion. In addition, we show that ttk binding correlates with neurogenic Notch signaling, and that specific ttk binding between castes is enriched for regulatory sites associated with hormonal function. Overall our findings elucidate a pathway of transcription factor binding leading to a repressive epigenetic axis that lies at the crux of development and hormonal signaling to define worker caste identity in C. floridanus.


2020 ◽  
Vol 8 (8) ◽  
pp. 1205
Author(s):  
Anaïs Larabi ◽  
Laurène Salesse ◽  
Charlotte Cordonnier ◽  
Lucie Etienne-Mesmin ◽  
Nicolas Barnich ◽  
...  

Adherent-invasive Escherichia coli (AIEC), which abnormally colonize the ileal mucosa of Crohn’s disease (CD) patients, are able to invade intestinal epithelial cells (IECs) and translocate through M cells overlying Peyer’s patches. The levels of microRNA (miRNA) and gene expression in IECs and M cells upon AIEC infection have not been investigated. Here, we used human intestinal epithelial Caco-2 monolayers and an in vitro M-cell model of AIEC translocation to analyze comprehensive miRNA and gene profiling under basal condition and upon infection with the reference AIEC LF82 strain. Our results showed that AIEC LF82 translocated through M cells but not Caco-2 monolayers. Both differential gene expression and miRNA profile in M cells compared to Caco-2 cells were obtained. In addition, AIEC infection induces changes in gene and miRNA profiles in both Caco-2 and M cells. In silico analysis showed that certain genes dysregulated upon AIEC infection were potential targets of AIEC-dysregulated miRNAs, suggesting a miRNA-mediated regulation of gene expression during AIEC infection in Caco-2, as well as M cells. This study facilitates the discovery of M cell-specific and AIEC response-specific gene-miRNA signature and enhances the molecular understanding of M cell biology under basal condition and in response to infection with CD-associated AIEC.


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