• 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.

• Journal of the Korean Chemical Society
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• v.46 no.2
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• pp.157-163
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• 2002

To identify RNA motifs interacting with $tRNA^{Val}$, a SELEX(Systematic Evolution of Ligands by Exponential Enrichment) was applied. Random DNA library which contains a region of ran-domized 48-mer oligonucleotide flanked by conserved sequ ence primers was transcribed into RNA pool using T7 RNA polymerase and RNA aptamers were selected with $tRNA^{Val}$ -immobilized affinity column through 14 rounds of SELEX. Some of the resulting aptamers contained a consensus sequence similar to the sequence in the loop regions of three rRNAs; C43GAAC47 sequence of 5S rRNA, G1491AAGU1495, G1379UUCC1383 sequence of 16S rRNA and C1064UUAG1068, G2110UGUA2114, C2480GACGG2485, A2600CAGU2604 sequence of 23S rRNA. These results suggest that $tRNA^{Val}$ can interact with 5S rRNA, 16S rRNA and 23S rRNA with variety in ribosome.

• The Plant Pathology Journal
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• v.24 no.3
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• pp.289-295
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• 2008

RNA-RNA interactions and the dynamic RNA conformations are important regulators in virus replication in several RNA virus systems and may also involved in the regulation of many important virus life cycle phases, including translation, replication, assembly, and switches in these important stages. The 5' non-translated region of Potato virus X(PVX) contains multiple cis-acting elements that facilitate various viral processes. It has previously been proposed that RNA-RNA interactions between various RNA elements present in PVX RNA genome are required for PVX RNA accumulation(Hu et al., 2007; Kim and Hemenway, 1999). This model was based on the potential base-pairing between conserved sequence elements at the upstream of subgenomic RNAs(sgRNAs) and at the 5' and 3' end of RNA genome. We now provide more evidence that RNA-RNA base-pairing between elements present at the 5' end and upstream of each sgRNA is required for efficient replication of genomic and subgenomic plus-strand RNA accumulation. Site-directed mutations introduced at the 5' end of plus-strand RNA replication defective mutant(${\Delta}12$) increasing base-pairing possibility with conserved sequence elements located upstream of each sgRNAs restored genomic and subgenomic plus-strand RNA accumulation and caused symptom development in inoculated Nicotiana benthamiana plants. Serial passage of a deletion mutant(${\Delta}8$) caused more severe symptoms and restored wild type sequences and thus retained possible RNA-RNA base-pairing. Altogether, these results indicate that the RNA element located at the 5' end of PVX genome involved in RNA-RNA interactions and play a key role in high-level accumulation of plus-strand RNA in vivo.

• Research in Plant Disease
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• v.10 no.4
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• pp.241-247
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• 2004

Recently, we reported a satellite RNA (Paf-satRNA) which is encapsidated in a pepper isolate of Cucumber mosaic virus (CMV-Paf) regulated symptom attenuation of the helper virus. To characterize mild symptom domain of Paf-satRNA, a series of chimeric cDNAs of satRNAs were created by using full-length cDNA clones of Paf-satRNA and a Pep-satRNA, chlorosis-inducing satRNA in pepper plants, and analyzed for determinants of symptom attenuation. When compared the nucleotide sequences, the 3' and 5' terminal sequences of the two wild-type (wt) satRNAs contained relatively conserved sequences which are the typical to CMV satRNA. Ten bases insertions were found in PepY-satRNA, and two variable regions, 81st to 113th and 183rd to 265th from the 5'-end, were located in the middle parts of the satRNAs. To delineate the attenuated symptom-related domain for the Paf-satRNA, in vitro transcripts RNAs transcribed from the wt cDNAs and constructed chimeric cDNAs were combined with genomic RNAs, RNA1, RNA2 and RNA3, of CMV-Fny and inoculated onto Nicotiana benthamiana plants. These transcripts were fully infectious onto the N. benthamiana and infectivity was confirmed by the RT-PCR. Chimeric Paf(H/N)-satRNA and PepY(N/A)-satRNA as well as Paf-satRNA induced very mild mosaic or symptomless infection on N. benthamiana. By contrast, typical mosaic symptom and stunting of infected plants were induced when PepY-satRNA, PepY(H/N)-satRNA and Paf(N/A)-satRNA were infected to N. benthamiana. Paf-satRNA coinfected with CMV-Fny RNAs induced very mild to sympomless on pepper plants whereas PepY-satRNA-infected pepper expressed typical chlorosis mosaic symptom. Two kinds of chimeric mutants, Paf(H/N)-satRNA and PepY(N/A)-satRNA, induced mild mosaic or symptomless infection onto pepper plants, while PepY(H/N)-satRNA and Paf(N/A)-satRNA showed typical chlorosis and mosaic symptom with stunting. This results suggest that mild symptom-related domain for the Paf-satRNA was located on HpaI-NarI region.

• BMB Reports
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• v.42 no.3
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• pp.125-130
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• 2009

Recent advances in RNA biology reveal unexpected diversity and complexity of cellular RNA metabolism. RNA-binding proteins (RBPs) are essential players in RNA metabolism, regulating RNA splicing, transport, surveillance, decay and translation. Aberrant expression of RBPs affects many steps of RNA metabolism, significantly altering expression of RNA. Thus, altered expression and dysfuncting of RBPs are implicated in the development of various diseases including cancer. In this minireview, we briefly describe emerging roles of RBPs as a global coordinator of post-transcriptional steps and altered RBP as a global generator of cancer related RNA alternative splicing. Identification and characterization of the RNA-RBP network would expand the scope of cellular RNA metabolism and provide novel anti-cancer therapeutic targets based on cancer specific RNA-RBP interaction.

• The Plant Pathology Journal
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• v.17 no.3
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• pp.115-122
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• 2001

Potato virus X (PVX) is a flexuous rod-shaped virus containing a single plus-strand RNA. Viral RNA synthesis is precisely regulated by regulatory viral sequences and by viral and/or host proteins. RNA sequence element as well as stable RNA stem-loop structure in the 5' end of the genome affect accumulation of genomic RNA and subgenomic RNA (sgRNA). The putative sgRNA promoter regions upstream of the PVX triple gene block (TB) and coat protein (CP) gene were critical for both TB and CP sgRNA accumulation. Mutations that disrupted complementarity between a region at the 5' end of the genomic RNA and the sequences located upstream of each sgRNA initiation site is important for PVX RNA accumulation. Compensatory mutations that restore complementarity restored sgRNA accumulation levels. However, the extent of reductions in RNA levels did not directly correlate with the degree of complementarity, suggesting that the sequences of these elements are also important. Gel-retardation assays showed that the 5' end of the positive-strand RNA formed an RNA-protein complex with cellular proteins, suggesting possible involvement of cellular proteins for PVX replication. Future studies on cellular protein binding to the PVX RNA and their role in virus replication will bring a fresh understanding of PVX RNA replication.

• BMB Reports
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• v.50 no.4
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• pp.226-231
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• 2017

At the post-transcriptional and translational levels, microRNA (miRNA) represses protein-coding genes via seed pairing to the 3' untranslated regions (UTRs) of mRNA. Although working models of miRNA-mediated gene silencing are successfully established using miRNA transfections and knockouts, the regulatory interaction between miRNA and long non-coding RNA (lncRNA) remain unknown. In particular, how the mRNA-resembling lncRNAs with 5' cap, 3' poly(A)-tail, or coding features, are regulated by miRNA is yet to be examined. We therefore investigated the functional interaction between miRNAs and lncRNAs with/without those features, in miRNA-transfected early zebrafish embryos. We observed that the greatest determinants of the miRNA-mediated silencing of lncRNAs were the 5' cap and 3' poly(A)-tails in lncRNAs, at both the post-transcriptional and translational levels. The lncRNAs confirmed to contain 5' cap, 3' poly(A)-tail, and the canonical miRNA target sites, were observed to be repressed in the level of both RNA and ribosome-protected fragment, while those with the miRNA target sites and without 5' cap and 3' poly(A)-tail, were not robustly repressed by miRNA introduction, thus suggesting a role as a miRNA-decoy.

• 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.

• Molecules and Cells
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• v.42 no.5
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• pp.379-385
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• 2019

Non-coding RNAs (ncRNAs) comprise various RNA species, including small ncRNAs and long ncRNAs (lncRNAs). ncRNAs regulate various cellular processes, including transcription and translation of target messenger RNAs. Recent studies also indicate that ncRNAs affect organismal aging and conversely aging influences ncRNA levels. In this review, we discuss our current understanding of the roles of ncRNAs in aging and longevity, focusing on recent advances using the roundworm Caenorhabditis elegans. Expression of various ncRNAs, including microRNA (miRNA), tRNA-derived small RNA (tsRNA), ribosomal RNA (rRNA), PIWI-interacting RNA (piRNA), circular RNA (circRNA), and lncRNA, is altered during aging in C. elegans. Genetic modulation of specific ncRNAs affects longevity and aging rates by modulating established aging-regulating protein factors. Because many aging-regulating mechanisms in C. elegans are evolutionarily conserved, these studies will provide key information regarding how ncRNAs modulate aging and lifespan in complex organisms, including mammals.

• Microbiology and Biotechnology Letters
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• v.30 no.1
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• pp.68-72
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• 2002

To obtain a yeast mutant with high RNA content and high growth rate, Saccharomyces cerevisiae MTY62 was mutated with ethylmethane sulfonate. Among the selected mutants that were sensitive to the high concentration of KCl, M40-10 strain was finally selected due to its rapid cell growth and high RNA content in the tube and baffled-flask cultures. In the batch culture of M40-10 mutant, the maximum specific growth rate ($\mu_{max}$) of $0.38 h^{-1}$ , RNA concentration of 3210 mg-RNA/1, and RNA content of 183 mg-RNA/g-DCW were obtained, which were 23%, 15%, and 12% increased levels, respectively, compared to those of MTY62 parent strain. The intermittent fed-batch culture of M40-10 strain resulted in the maximum cell concentration of 35.6 g-DCW/1, RNA concentration of 5677 mg/1, and RNA content of 160 mg-RNA/g-DCW. Through the constant fed-batch culture, the maximum cell concentration of 46.4 g-DCW/1, RNA concentration of 6270 mg-RNA/1, and RNA content of 135 mg-RNA/g-DCW were obtained. At the 20 h culture time in the fed-batch cultures of M40-10 strain, the cell and RNA concentrations were increased by 30% and 10%, respectively, over the parent strain MTY62. In addition, it was also found that the accumulated RNA within the mutant cell was not degraded until the end of fed-batch cultivation, indicating that the M40-10 cell is a mutant with weak acidic RNase activity.y.