• 한국미생물생명공학회:학술대회논문집
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• 한국미생물생명공학회 2001년도 Proceedings of 2001 International Symposium
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• pp.83-89
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• 2001

Recent advances in the structural and molecular biology uncovered that a set of translation factors resembles a tRNA shape and, in one case, even mimics a tRNA function for deciphering the genetic ：ode. Nature must have evolved this 'art' of molecular mimicry between protein and ribonucleic acid using different protein architectures to fulfill the requirement of a ribosome 'machine'. Termination of protein synthesis takes place on the ribosomes as a response to a stop, rather than a sense, codon in the 'decoding' site (A site). Translation termination requires two classes of polypeptide release factors (RFs)： a class-I factor, codon-specific RFs (RFI and RF2 in prokaryotes; eRFI in eukaryotes), and a class-IT factor, non-specific RFs (RF3 in prokaryotes; eRF3 in eukaryotes) that bind guanine nucleotides and stimulate class-I RF activity. The underlying mechanism for translation termination represents a long-standing coding problem of considerable interest since it entails protein-RNA recognition instead of the well-understood codon-anticodon pairing during the mRNA-tRNA interaction. Molecular mimicry between protein and nucleic acid is a novel concept in biology, proposed in 1995 from three crystallographic discoveries, one, on protein-RNA mimicry, and the other two, on protein-DNA mimicry. Nyborg, Clark and colleagues have first described this concept when they solved the crystal structure of elongation factor EF- Tu：GTP：aminoacyl-tRNA ternary complex and found its overall structural similarity with another elongation factor EF-G including the resemblance of part of EF-G to the anticodon stem of tRNA (Nissen et al. 1995). Protein mimicry of DNA has been shown in the crystal structure of the uracil-DNA glycosylase-uracil glycosylase inhibitor protein complex (Mol et al. 1995; Savva and Pear 1995) as well as in the NMR structure of transcription factor TBP-TA $F_{II}$ 230 complex (Liu et al. 1998). Consistent with this discovery, functional mimicry of a major autoantigenic epitope of the human insulin receptor by RNA has been suggested (Doudna et al. 1995) but its nature of mimic is. still largely unknown. The milestone of functional mimicry between protein and nucleic acid has been achieved by the discovery of 'peptide anticodon' that deciphers stop codons in mRNA (Ito et al. 2000). It is surprising that it took 4 decades since the discovery of the genetic code to figure out the basic mechanisms behind the deciphering of its 64 codons.

• Bulletin of the Korean Chemical Society
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• 제26권12호
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• pp.2033-2037
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• 2005

In vitro selection was used to isolate $Mg^{2+}$-dependent self-cleaving ribozymes with cis-cleavage activity from a pre-tRNA library having 40-mer random sequences attached to 5'-end of E. coli $tRNA^{Phe}$. After 8 rounds of SELEX (Systematic Evolution of Ligands by Exponential Enrichment), RNA molecules which can self-cleave at the high concentration of $Mg^{2+}$ were isolated. The selected ribozymes can carry out the self-cleavage reaction in the presence of 100 mM $Mg^{2+}$ but not in 10 mM $Mg^{2+}$. The cleavage sites of the ribozymes are located at +3 and +4 of $tRNA^{Phe}$, compared with +1 position of 5'-end cleavage site of pre-tRNA by RNase P. New RNA constructs deprived of its D stem-loop, anticodon stem-loop, variable loop and T stem-loop, respectively showed the cleavage specificity identical to a ribozyme having the intact tRNA structure. Also, the new ribozyme fused with both a ribozyme and $tRNA^{Leu}$ showed the cleavage activities at the various sites within its sequences, different from two sites of position +3 and +4 observed in the ribozyme with $tRNA^{Phe}$. Our results suggest that the selected ribozyme is not structural-specific for tRNA.

• BMB Reports
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• 제50권4호
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• pp.194-200
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• 2017

Eukaryotic gene expression is precisely regulated at all points between transcription and translation. In this review, we focus on translational control mediated by the 3'-untranslated regions (UTRs) of mRNAs. mRNA 3'-UTRs contain cis-acting elements that function in the regulation of protein translation or mRNA decay. Each RNA binding protein that binds to these cis-acting elements regulates mRNA translation via various mechanisms targeting the mRNA cap structure, the eukaryotic initiation factor 4E (eIF4E)-eIF4G complex, ribosomes, and the poly (A) tail. We also discuss translation-mediated regulation of mRNA fate.

• Communications for Statistical Applications and Methods
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• 제22권2호
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• pp.181-199
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• 2015

In a short history, RNA-seq data have established a revolutionary tool to directly decode various scenarios occurring on whole genome-wide expression profiles in regards with differential expression at gene, transcript, isoform, and exon specific quantification, genetic and genomic mutations, and etc. RNA-seq technique has been rapidly replacing arrays with seq-based platform experimental settings by revealing a couple of advantages such as identification of alternative splicing and allelic specific expression. The remarkable characteristics of high-throughput large-scale expression profile in RNA-seq are lied on expression levels of read counts, structure of correlated samples and genes, larger number of genes compared to sample size, different sampling rates, inevitable systematic RNA-seq biases, and etc. In this study, we will comprehensively review how robust Bayesian and non-parametric methods have a better performance than classical statistical approaches by explicitly incorporating such intrinsic RNA-seq specific features with flexible and more appropriate assumptions and distributions in practice.

• Journal of Cancer Prevention
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• 제22권4호
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• pp.203-210
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• 2017

After transcription, RNAs are always associated with RNA binding proteins (RBPs) to perform biological activities. RBPs can interact with target RNAs in sequence- and structure-dependent manner through their unique RNA binding domains. In development and progression of carcinogenesis, RBPs are aberrantly dysregulated in many human cancers with various mechanisms, such as genetic alteration, epigenetic change, noncoding RNA-mediated regulation, and post-translational modifications. Upon deregulation in cancers, RBPs influence every step in the development and progression of cancer, including sustained cell proliferation, evasion of apoptosis, avoiding immune surveillance, inducing angiogenesis, and activating metastasis. To develop therapeutic strategies targeting RBPs, RNA interference-based oligonucleotides or small molecule inhibitors have been screened based on reduced RBP-RNA interaction and changed level of target RNAs. Identification of binding RNAs with high-throughput techniques and integral analysis of multiple datasets will help us develop new therapeutic drugs or prognostic biomarkers for human cancers.

• Journal of Microbiology
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• 제33권2호
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• pp.136-141
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• 1995

From a cluster of structural rRNA genes which has previsouly been cloned (Hwang and Kim, in submission; J. Microbiol. Biotechnol.), a 1.0-kb Eco RI fragment of DNA which shows significant homology to the 25S and rRNA s of Tricholoma matsutake was used for sequence analysis. Nucleotide sequence was bidirectionally determined using delection series of the DNA fragment. Comparing the resultant 1016-base sequence with sequences in the database, both the 3'end of 25S-rRNA gene and 5S rRNA gene were searched. The 5S rRNA gene is 118-bp in length and is located 158-bp downstream of 3'end of the 25S rRNA gene. IGSI and IGS2 (partial) sequences are also contained in the fragment. Multiple alignment of the 5S rRNA sequences was carried out with 5S rRNA sequences from some members of the subdivision Basidiomycotina obtained from the database. Polygenetic analysis with distance matrix established by Kimura's 2-parameter method and phylogenetic tree by UPGMA method proposed that T. matsutake is closely related to efibulobasidium allbescens. Secondary structure of 5S rRNA was also hypothesized to show similar topology with its generally accepted eukaryotic counterpart.

• Journal of Microbiology and Biotechnology
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• 제11권2호
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• pp.251-258
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• 2001

In Gram(+) bacteria and organelles in higher eukarotes, $Gln-tRNA^{Gln}$ utilized for protein biosynthesis is formed by a tRNA-dependent amino acid transformation using mischarged $Gln-tRNA^{Gln}$ as the intermediate. In this study, the gatCAB gene encoding $Gln-tRNA^{Gln}$ amidotransferase (Glu-AdT) of Staphylococcus aureus was cloned and its nucleotide sequence wa determined. The S. aureus gatCAB gene was organized in an operon structure consisting of three open reading frames (gatC, gatA, and gatB), similar to that of Bacillus subtilis. The gene sequences for the A and B subunits of$Gln-tRNA^{Gln}$ amidotransferase showed significant homology (77 and 87% homology with amino acid sequence) with the gatA and gatB genes of B. subtilis, yet the C subunit (gatC) showed a relatively lowe homology with the B. subtilis gatC gene and other orthologues. The cloned S. aureus <$Gln-tRNA^{Gln}$ amidotransferase gene was highly expressed in Escherichia coli, and the resulting crude enzyme could convert misacylated <$Gln-tRNA^{Gln}$ into $Gln-tRNA^{Gln}$ in vitro.

• Bulletin of the Korean Chemical Society
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• 제34권3호
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• pp.837-850
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• 2013

Bovine viral diarrhea virus (BVDV), a major pathogen of cattle, is a well-characterized pestivirus which has been used as a good model virus for HCV. The RNA-dependent RNA polymerase (RdRp) plays a key role in the RNA replication process, thus it has been targeted for antivirus drugs. We employed two-dimensional quantitative structure-activity relationship (2D-QSAR) and molecular field analysis (MFA) to identify the molecular substructure requirements, and the particular characteristics resulted in increased inhibitory activity for the known series of compounds to act as effective BVDV inhibitors. The 2D-QSAR study provided the rationale concept for changes in the structure to have more potent analogs focused on the class of arylazoenamines, benzimidazoles, and acridine derivatives with an optimal subset of descriptors, which have significantly contributed to overall anti-BVDV activity. MFA represented the molecular patterns responsible for the actions of antiviral compound at their receptors. We conclude that the polarity and the polarizability of a molecule play a main role in the inhibitory activity of BVDV inhibitors in the QSAR modeling.

• Molecules and Cells
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• 제21권3호
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• pp.330-336
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• 2006

Since its identification in 1989, hepatitis C virus has been the subject of extensive research. The biology of the virus and the development of antiviral drugs are closely related. The RNA polymerase activity of nonstructural protein 5B was first demonstrated in 1996. NS5B is believed to localize to the perinuclear region, forming a replicase complex with other viral proteins. It has a typical polymerase structure with thumb, palm, and finger domains encircling the active site. A de novo replication initiation mechanism has been suggested. To date, many small molecule inhibitors are known including nucleoside analogues, non-nucleoside analogues, and pyrophosphate mimics. NS5B interacts with other viral proteins such as core, NS3, 4A, 4B, and 5A. The helicase activity of NS3 seems necessary for RNA strand unwinding during replication, with other nonstructural proteins performing modulatory roles. Cellular proteins interacting with NS5B include VAMP-associated proteins, heIF4AII, hPLIC1, nucleolin, PRK2, ${\alpha}$-actinin, and p68 helicase. The interactions of NS5B with these proteins might play roles in cellular trafficking, signal transduction, and RNA polymerization, as well as the regulation of replication/translation processes.

• 대한화학회지
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• 제39권9호
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• pp.734-740
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• 1995

Xanthomonas palargonii 5S rRNA의 일차구조 및 이차구조를 결정하고 에틸니트로소 우레아, Pb2+, 황산 이메틸 , 피로탄산 이에틸 들의 화학 탐침과 몇 가지 효소 탐침을 사용하여 고차원 구조를 분석하였다. 에틸니트로소 우레아는 삼차 상호작용에 관련되는 포스포디에스테르 결합을 조사하는데 사용되었다. Mg2+이 있을 때 에틸니트로소 우레아에 의한 변형에 대해서 저항성이 있는 자리는 불안정한 d 나선의 Nucleotides G72, A73, G75, A78, G98, G100, A101 들, c고리의 C36, C37, C39, C41들, 그리고 C 줄기의 A29, G33 들이다.이러한 결과와 Pb2+에 의한 가수분해 반응과 화학 탐침과 효소 탐침을 사용하여 얻은 결과들을 종합해 봄으로써 5S 의 b-C 구역과 d 나선 구역은 5S rRNA의 삼차 상호작용에서 돌쩌귀의 구실을 할 것으로 추정할 수 있었다.