• Journal of Genetic Medicine
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• 제10권1호
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• pp.27-32
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• 2013

Post-transcriptional nucleotide sequence modification of transcripts by RNA editing is an important molecular mechanism in the regulation of protein function and is associated with a variety of human disease phenotypes. Identification of RNA editing sites is the basic step for studying RNA editing. Databases and bioinformatics resources are used to annotate and evaluate as well as identify RNA editing sites. No method is free of limitations. Correctly establishing an analytic pipeline and strategic application of both experimental and bioinformatics methods constitute the first step in investigating RNA editing. This review summarizes modern bioinformatics approaches and related resources for RNA editing research.

• The Korean Journal of Physiology and Pharmacology
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• 제23권3호
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• pp.181-189
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• 2019

Curcumin, an active ingredient of Curcuma longa L., can reduce the concentration of low-density lipoproteins in plasma, in different ways. We had first reported that curcumin exhibits hypocholesterolemic properties by improving the apolipoprotein B (apoB) mRNA editing in primary rat hepatocytes. However, the role of curcumin in the regulation of apoB mRNA editing is not clear. Thus, we investigated the effect of curcumin on the expression of multiple editing components of apoB mRNA cytidine deamination to uridine (C-to-U) editosome. Our results demonstrated that treatment with $50{\mu}M$ curcumin markedly increased the amount of edited apoB mRNA in primary mouse hepatocytes from 5.13%-8.05% to 27.63%-35.61%, and significantly elevated the levels of the core components apoB editing catalytic polypeptide-1 (APOBEC-1), apobec-1 complementation factor (ACF), and RNA-binding-motif-protein-47 (RBM47), as well as suppressed the level of the inhibitory component glycine-arginine-tyrosine-rich RNA binding protein. Moreover, the increased apoB RNA editing by $50{\mu}M$ curcumin was significantly reduced by siRNA-mediated APOBEC-1, ACF, and RBM47 knockdown. These findings suggest that curcumin modulates apoB mRNA editing by coordinating the multiple editing components of the edito-some in primary hepatocytes. Our data provided evidence for curcumin to be used therapeutically to prevent atherosclerosis.

• 생명과학회지
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• 제8권2호
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• pp.203-207
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• 1998

본 연구는 옥수수에서 분리한 미토콘드리아에서 NADH-dehydrogenase 유전자 (subunit 4)의 cDNA를 RT-PCR의 방법을 사용하여 조제 한 ㅜ 염기서열 수행한 경과 특이한 점을 감지 할 수 있었다. 일반적인 RNA cditing은 C에서 U로 또는 U에서 C로 치환되는 현장으로 옥수수의 NAD4유전자에서도 이러한 editing 형상이 일어나는 것을 발견하였다. 또는 T가 G로 그리고 G 가 A로 변화되는 특이한 부분들이 생성되는 것을 관찰하였다. 이러한 RNA ediring은 주로 exon 1과 exon 4 에 많이 일어나며, 염기 치환되는 부분들은 에서늬 NAD4유전자의 RNA edting site들과 일피하지 않은 점으로 미루어 보아 RNA editing 현상은 무작의로 생성된다고 본다.된다고 본다.

• 산업기술연구
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• 제24권B호
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• pp.139-142
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• 2004

To identify conserved structural or functional subunit(s) in the CP1 (editing) domains of class Ia tRNA synthetases, five available structures were compared and analyzed. Through sequence alignments of the CP1 domains, three conserved regions were found near the amino acid binding site in the editing domain. Structural overlapping of the three subunits clearly showed that there exist three common structural subunits in all of the five editing RS structures. The new alignment suggests a translocation movement of the CP1 domain caused by the binding with tRNA. Based on the experimental and modeling results, it is proposed that subunits 1 and 3 accommodate the incoming amino acid binding, while subunit 2 contributes to the interactions with the adenosine ring of the A76 to stabilize the overall tRNA binding.. Since these subunits are critical for the editing reaction, we expect that these key structures should be conserved through all class Ia editing RSs.

• Molecules and Cells
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• 제46권6호
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• pp.351-359
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• 2023

Deamination of adenine or cytosine in RNA, called RNA editing, is a constitutively active and common modification. The primary role of RNA editing is tagging RNA right after its synthesis so that the endogenous RNA is recognized as self and distinguished from exogenous RNA, such as viral RNA. In addition to this primary function, the direct or indirect effects on gene expression can be utilized in cancer where a high level of RNA editing activity persists. This report identified actin-related protein 2/3 complex inhibitor (ARPIN) as a target of ADAR1 in breast cancer cells. Our comparative RNA sequencing analysis in MCF7 cells revealed that the expression of ARPIN was decreased upon ADAR1 depletion with altered editing on its 3'UTR. However, the expression changes of ARPIN were not dependent on 3'UTR editing but relied on three microRNAs acting on ARPIN. As a result, we found that the migration and invasion of cancer cells were profoundly increased by ADAR1 depletion, and this cellular phenotype was reversed by the exogenous ARPIN expression. Altogether, our data suggest that ADAR1 suppresses breast cancer cell mobility via the upregulation of ARPIN.

• BMB Reports
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• 제55권6호
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• pp.251-258
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• 2022

Innovative genome editing techniques developed in recent decades have revolutionized the biomedical research field. Liver is the most favored target organ for genome editing owing to its ability to regenerate. The regenerative capacity of the liver enables ex vivo gene editing in which the mutated gene in hepatocytes isolated from the animal model of genetic disease is repaired. The edited hepatocytes are injected back into the animal to mitigate the disease. Furthermore, the liver is considered as the easiest target organ for gene editing as it absorbs almost all foreign molecules. The mRNA vaccines, which have been developed to manage the COVID-19 pandemic, have provided a novel gene editing strategy using Cas mRNA. A single injection of gene editing components with Cas mRNA is reported to be efficient in the treatment of patients with genetic liver diseases. In this review, we first discuss previously reported gene editing tools and cases managed using them, as well as liver diseases caused by genetic mutations. Next, we summarize the recent successes of ex vivo and in vivo gene editing approaches in ameliorating liver diseases in animals and humans.

• Bulletin of the Korean Chemical Society
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• 제28권2호
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• pp.207-210
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• 2007

To identify structural or functional common subunit(s) in the CP1 (editing) domains of class Ia tRNA synthetases, five available structures were compared and analyzed. Through the sequence alignments and structural overlapping of the CP1 domains, three conserved regions were identified near the amino acid binding site in the editing domain. Structural overlapping of the three subunits clearly showed the existence of three common structural subunits in all of the five editing RS structures. Based on the established experimental results and our modeling results, it is proposed that subunits 1 and 3 accommodate the incoming amino acid binding, while subunit 2 contributes to the interactions with the adenosine ring of the A76 to stabilize the overall tRNA binding. Since these subunits are critical for the editing reaction, we expect that these key structures should be conserved through the most class Ia editing RSs.

• Molecules and Cells
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• 제44권12호
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• pp.911-919
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• 2021

The virus-induced genome editing (VIGE) system aims to induce targeted mutations in seeds without requiring any tissue culture. Here, we show that tobacco rattle virus (TRV) harboring guide RNA (gRNA) edits germ cells in a wild tobacco, Nicotiana attenuata, that expresses Streptococcus pyogenes Cas9 (SpCas9). We first generated N. attenuata transgenic plants expressing SpCas9 under the control of 35S promoter and infected rosette leaves with TRV carrying gRNA. Gene-edited seeds were not found in the progeny of the infected N. attenuata. Next, the N. attenuata ribosomal protein S5 A (RPS5A) promoter fused to SpCas9 was employed to induce the heritable gene editing with TRV. The RPS5A promoter-driven SpCas9 successfully produced monoallelic mutations at three target genes in N. attenuata seeds with TRV-delivered guide RNA. These monoallelic mutations were found in 2%-6% seeds among M₁ progenies. This editing method provides an alternative way to increase the heritable editing efficacy of VIGE.

• BMB Reports
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• 제50권1호
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• pp.20-24
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• 2017

Clustered regularly-interspaced short palindromic repeats (CRISPR) is a new and effective genetic editing tool. CRISPR was initially found in bacteria to protect it from virus invasions. In the first step, specific DNA strands of virus are identified by guide RNA that is composed of crRNA and tracrRNA. Then RNAse III is required for producing crRNA from pre-crRNA. In The second step, a crRNA:tracrRNA:Cas9 complex guides RNase III to cleave target DNA. After cleavage of DNA by CRISPR-Cas9, DNA can be fixed by Non-Homologous End Joining (NHEJ) and Homology Directed Repair (HDR). Whereas NHEJ is simple and random, HDR is much more complex and accurate. Gene editing by CRISPR is able to be applied to various biological field such as agriculture and treating genetic diseases in human.

• Genomics & Informatics
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• 제17권3호
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• pp.23.1-23.6
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• 2019

The acquisition of somatic mutations is the most common event in cancer. Neoantigens expressed from genes with mutations acquired during carcinogenesis can be tumor-specific. Since the immune system recognizes tumor-specific peptides, they are potential targets for personalized neoantigen-based immunotherapy. However, the discovery of druggable neoantigens remains challenging, suggesting that a deeper understanding of the mechanism of neoantigen generation and better strategies to identify them will be required to realize the promise of neoantigen-based immunotherapy. Alternative splicing and RNA editing events are emerging mechanisms leading to neoantigen production. In this review, we outline recent work involving the large-scale screening of neoantigens produced by alternative splicing and RNA editing. We also describe strategies to predict and validate neoantigens from RNA sequencing data.