• Journal of KIISE:Computing Practices and Letters
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• v.16 no.10
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• pp.980-984
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• 2010

Exploring microRNA (miRNA) and mRNA regulatory interactions may give new insights into diverse biological phenomena. Recently, miRNAs have been discovered as important regulators that play a major role in various cellular processes. Therefore, it is essential to identify functional interactions between miRNAs and mRNAs for understanding the context- dependent activities of miRNAs in complex biological systems. While elucidating complex miRNA-mRNA interactions has been studied with experimental and computational approaches, it is still difficult to infer miRNA-mRNA regulatory modules. Here we present a novel method, termed layered hypernetworks (LHNs), for identifying functional miRNA-mRNA interactions from heterogeneous expression data. In experiments, we apply the LHN model to miRNA and mRNA expression profiles on multiple cancers. The proposed method identifies cancer-specific miRNA-mRNA interactions. We show the biological significance of the discovered miRNA- mRNA interactions.

• BMB Reports
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• v.48 no.7
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• pp.367-368
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• 2015

It has long been thought that glucocorticoid receptor (GR) functions as a DNA-binding transcription factor in response to its ligand (a glucocorticoid) and thus regulates various cellular and physiological processes. It is also known that GR can bind not only to DNA but also to mRNA; this observation points to the possible role of GR in mRNA metabolism. Recent data revealed a molecular mechanism by which binding of GR to target mRNA elicits rapid mRNA degradation. GR binds to specific RNA sequences regardless of the presence of a ligand. In the presence of a ligand, however, the mRNA-associated GR can recruit PNRC2 and UPF1, both of which are specific factors involved in nonsense-mediated mRNA decay (NMD). PNRC2 then recruits the decapping complex, consequently promoting mRNA degradation. This mode of mRNA decay is termed "GR-mediated mRNA decay" (GMD). Further research demonstrated that GMD plays a critical role in chemotaxis of immune cells by targeting CCL2 mRNA. All these observations provide molecular insights into a previously unappreciated function of GR in posttranscriptional regulation of gene expression. [BMB Reports 2015; 48(7): 367-368]

• Molecules and Cells
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• v.46 no.1
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• pp.41-47
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• 2023

The rapid development of mRNA vaccines has contributed to the management of the current coronavirus disease 2019 (COVID-19) pandemic, suggesting that this technology may be used to manage future outbreaks of infectious diseases. Because the antigens targeted by mRNA vaccines can be easily altered by simply changing the sequence present in the coding region of mRNA structures, it is more appropriate to develop vaccines, especially during rapidly developing outbreaks of infectious diseases. In addition to allowing rapid development, mRNA vaccines have great potential in inducing successful antigen-specific immunity by expressing target antigens in cells and simultaneously triggering immune responses. Indeed, the two COVID-19 mRNA vaccines approved by the U.S. Food and Drug Administration have shown significant efficacy in preventing infections. The ability of mRNAs to produce target proteins that are defective in specific diseases has enabled the development of options to treat intractable diseases. Clinical applications of mRNA vaccines/therapeutics require strategies to safely deliver the RNA molecules into targeted cells. The present review summarizes current knowledge about mRNA vaccines/ therapeutics, their clinical applications, and their delivery strategies.

• Korean Journal of Microbiology
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• v.26 no.1
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• pp.27-31
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• 1988

Biosynthesis and processing of cytoplasmic mRNA from heterogenous nuclear RNA (hn-RNA) in Aspergillus phoenicis were studied by $^{3}H$-uridine labeling and synchronous culture techniques during their life cycle. Incorporations of $^{3}H$-uridine into hn-RNA and mRNA were most rapid in vesicle-phialide fromation stage and diminished in hyphal growth stage. The processing of cytoplasmic mRNA from hn-RNA was proceeded more rapidly in hyphal growth and conidiophore formation stages than in conidia and vesicle-phialide formation stages. The specific radioactivities of hn-RNA and mRNA were very high in vesicle-phialide formation stage.

• Fisheries and Aquatic Sciences
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• v.13 no.1
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• pp.56-62
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• 2010

To determine whether long double-stranded RNA (dsRNA) induces RNA interference and type I interferon (IFN) responses in fish, long dsRNAs encoding enhanced green fluorescent protein (EGFP), GFPuv, and polyinosinic-polycytidylic acid sequences were co-injected with an EGFP expressing plasmid, into rock bream (Oplegnathus fasciatus). We investigated the EGFP mRNA and protein levels, and the transcriptional responses of dsRNA-dependent protein kinase and Mx1 genes. Long dsRNAs were strong inducers of a type I IFN response in rock bream, resulting in nonspecific suppression of exogenous gene expression. Furthermore, sequence-specific knockdown of exogenous gene expression at the mRNA level was detected at an early phase (24 h). These results suggested that long dsRNA may inhibit exogenous gene expression through an early mRNA interference response and a later type I IFN response in fish.

• Biomedical Science Letters
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• v.20 no.3
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• pp.162-167
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• 2014

Tuberculosis (TB) is one of the major global health problems and it has been estimated that in 5~10% of Mycobacterium tuberculosis (MTB)-infected individuals, the infection progresses to an active disease. Numerous cytokines and chemokines regulate immunological responses at cellular level including stimulation and recruitment of wide range of cells in immunity and inflammation. In the present study, the mRNA expression levels of eight host immune markers containing of IFN-${\gamma}$, TNF-${\alpha}$, IL-2R, IL-4, IL-10, CXCL9, CXCL10, and CXCL11 in whole blood cells from active pulmonary TB patients were measured after T-cell mitogen (PHA) and MTB specific antigens (ESAT-6, CFP-10, and TB7.7). Among the TH1-type factors, IFN-${\gamma}$ mRNA expression was peaked at 4 h, TNF-${\alpha}$ and IL-2R mRNA expression was significantly high at the late time points (24 h) in active TB patients, TH2-type cytokine (IL4 and IL10) mRNA expression levels in both active TB and healthy controls samples did not changed significantly, and the mRNA expression of the three IFN-${\gamma}$-induced chemokines (CXCL9, CXCL10, and CXCL11) were peaked at the late time points (24 h) in active TB patients after MTB specific antigen stimulation. In conclusion, the mRNA expression patterns of the TB-related immune markers in response to the T-cell mitogen (PHA) differed from those in response to MTB specific antigens and these findings may helpful for understanding the relationship between MTB infection and host immune markers in a transcripts level.

• Journal of dental hygiene science
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• v.13 no.3
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• pp.321-329
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• 2013

Although it has been reported that lysyl oxidase (LOX) is involved in odontoblastic differentiation, the role of LOX on odontoblastic differentiation by hydrogen peroxide ($H_2O_2$) have not been clarified. In the present study, we investigated whether $H_2O_2$, reactive oxygen species (ROS), is modulated the messenger RNA (mRNA) expression and activity of LOX during odontoblastic differentiation of human dental pulp (HDP) cells. The mRNA expression was quantified by reverse transcriptase polymerase chain reaction (RT-PCR) analysis, and LOX enzyme activity was measured by high sensitive fluorescent assay. Expression of the odontoblastic differentiation marker genes were assessed in the presence and absence of specific small interfering RNAs (siRNAs) of the LOX and LOXL. The $H_2O_2$-induced mRNA expression of LOX family was significant reduction of LOX, LOXL, and LOXL3 mRNA levels in HDP cells. LOX enzyme activity was increased at $H_2O_2$ 0.3 mM for 24 hours. The mRNA expression of alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN) was inhibited by LOX- and LOXL-specific siRNAs whereas the mRNA expression of dentin matrix protein1 (DMP1), and dentin sialophosphoprotein (DSPP) was inhibited by LOX-specific siRNA. In LOX enzyme activity, siRNA-induced knockdown of both LOX and LOXL inhibited the total amine oxidase activity in HDP cells, as in the case of mRNA expression. In conclusion, the essential role of $H_2O_2$ on odontoblastic differentiation suggests that its regulation by LOX may have pharmacologic importance in HDP cells.

• Bioinformatics and Biosystems
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• v.2 no.1
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• pp.17-23
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• 2007

Shot interfering RNA (siRNA) can be used to silence specific gene expression and have many potential therapeutic applications. However, how to design an effective siRNA is still not clear. Highly effective siRNA has sequence-specific properties which are low G/C content, low internal stability at the sense strand 3'-terminus, sense strand base bias(position 1 is G/C, position 19 is /AU). Recently, mRNA secondary structure playsan important role in RNAi. Target site of siRNA in high-ordered structure (i.e hairpin loop, multi loop) or base pair of many hydrogen bonds dramatically reduce function of siRNA mediated gene silencing. Possible off-target effects of siRNA is detecting from BLAST search.

• Tuberculosis and Respiratory Diseases
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• v.56 no.4
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• pp.393-404
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• 2004

Background : Nucleic acid hybridization has become an essential technique in the development of our understanding of gene structure and function. The quantitative analysis of hybridization has been used in the measurement of genome complexity and gene copy number. The filter hybridization assay is rapid, sensitive and can be used to measure RNAs complementary to any cloned DNA sequence. Methods : The authors assessed the accuracy, linearity, correlation coefficient and specificity of the hybridization depending on the added dose(0, 1, 5, and $10{\mu}g$) of non-specific rat spleen RNA to hybridization of surfactant protein A mRNA. Filter hybridization assays were used to obtain the equation of standard curve and thereby to quantitate the mRNA quantitation. Results : 1. Standard curve equation of filter hybridization assay between counts per minute (X) and spleen RNA input (Y) was Y=0.13X-19.35. Correlation coefficient was 0.98. 2. Standard curve equation of filter hybridization assay between counts per minute (X) and surfactant protein A mRNA transcript input (Y) was Y=0.00066X-0.046. Correlation coefficient was 0.99. 3. Standard curve equation of filter hybridization assay between counts per minute (X) and surfactant protein A mRNA transcript input (Y) after the addition of $1{\mu}g$ spleen RNA was Y=0.00056X-0.051. Correlation coefficient was 0.99. 4. Standard curve equation of filter hybridization assay between counts per minute (X) and surfactant protein A mRNA transcript input (Y) after the addition of $5{\mu}g$ spleen RNA was Y=0.00065X-0.088. Correlation coefficient was 0.99. 5. Standard curve equation of filter hybridization assay between counts per minute (X) and surfactant protein A mRNA transcript input (Y) after the addition of $10{\mu}g$ spleen RNA was Y=0.00051X-0.10. Correlation coefficient was 0.99. Conclusions : Comparison of cpm/filter in a linear range allowed accurate and reproducible estimation of surfactant protein A mRNA copy number irrespective of the addition dosage of non-specific rat spleen RNA over the range $0-10{\mu}g$.

• Korean Journal of Microbiology
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• v.30 no.3
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• pp.177-180
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• 1992

Among 120 U. maydis strains isolated in Korea 14 different strains containing specific viral dsRNA segments were analyzed for the distribution of dsRNA and the production of toxin protein. Several distinctive dsRNA patterns were identified, 9 cases of P type with typical H, M and L ds RNA and one case of non-P-type, the frequency of a specific isolate was decreased with increasing number of dsRNA segments. The presence of dsRNA had no effect on the cultural or morphological phenotype of the host. Two isolates containing P type dsRNA segments appeared to produce toxin protein (killer strains) which inhibited the growth of 4 isolates (sensitive strain) with different susceptibility. Two killer strains contain unique M dsRNA segment which may code for toxin protein. However, the presence of toxin-sensitive strains among dsRNA-free isolates was similar to that of ds RNA containing strains.