• 제목/요약/키워드: splicing

검색결과 384건 처리시간 0.021초

Cancer-Specific Induction of Adenoviral E1A Expression by Group I Intron-Based Trans-Splicing Ribozyme

  • Won, You-Sub;Lee, Seong-Wook
    • Journal of Microbiology and Biotechnology
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    • 제22권3호
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    • pp.431-435
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    • 2012
  • In this study, we describe a novel approach to achieve replicative selectivity of conditionally replicative adenovirus that is based upon trans-splicing ribozyme-mediated replacement of cancer-specific RNAs. We developed a specific ribozyme that can reprogram human telomerase reverse transcriptase (hTERT) RNA to induce adenoviral E1A gene expression selectively in cancer cells that express the RNA. Western blot analysis showed that the ribozyme highly selectively triggered E1A expression in hTERT-expressing cancer cells. RT-PCR and sequencing analysis indicated that the ribozyme-mediated E1A induction was caused via a high fidelity trans-splicing reaction with the targeted residue in the hTERT-expressing cells. Moreover, reporter activity under the control of an E1A-dependent E3 promoter was highly transactivated in hTERT-expressing cancer cells. Therefore, adenovirus containing the hTERT RNA-targeting trans-splicing ribozyme would be a promising anticancer agent through selective replication in cancer cells and thus specific destruction of the infected cells.

Specificity of Intracellular Trans-Splicing Reaction by hTERT-Targeting Group I Intron

  • Jung, Heung-Su;Kwon, Byung-Su;Lee, Seong-Wook
    • Genomics & Informatics
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    • 제3권4호
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    • pp.172-174
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    • 2005
  • Recent anti-cancer approaches have been based to target tumor-specifically associated and/or causative molecules such as RNAs or proteins. As this specifically targeted anti-cancer modulator, we have previously described a novel human cancer gene therapeutic agent that is Tetrahymena group I intron-based trans-splicing ribozyme which can reprogram and replace human telomerase reverse transcriptase (hTERT) RNA to selectively induce tumor-specific cytotoxicity in cancer cells expressing the target RNA. Moreover, the specific ribozyme has been shown to efficiently retard tumor tissues in xenograft mice which had been inoculated with hTERT-expressing human cancer cells. In this study, we assessed specificity of trans-splicing reaction in cells to evaluate the therapeutic feasibility of the specific ribozyme. In order to analyze the trans-spliced products by the specific ribozyme in hTERT-positive cells, RT, 5'-end RACE-PCR, and sequencing reactions of the spliced RNAs were employed. Then, whole analyzed products resulted from reactions only with the hTERT RNA. This study suggested that the developed ribozyme perform highly specific RNA replacement of the target RNA in cells, hence trans-splicing ribozyme will be one of specific agents for genetic approach to revert cancer.

추철근 겹침이음된 철근콘크리트 교각의 보강에 의한 내진성능평가 (Seismic Performance and Retrofit of Reinforced Concrete Bridge Piers with Spliced Longitudinal Steels)

  • 정영수;이재형
    • 한국지진공학회:학술대회논문집
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    • 한국지진공학회 2001년도 추계 학술발표회 논문집 Proceedings of EESK Conference-Fall 2001
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    • pp.179-186
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    • 2001
  • It has been known that lap splicing in the longitudinal reinforcement of bridge columns is not desirable for seismic performance, but it is sometimes unavoidable. Lap splices were usually be located in the plastic hinge region of most bridge columns that were constructed before the adoption of the seismic design provision of Korea Bridge Design Specification on 1992. This research is to evacuate the seismic performance of reinforced concrete bridge piers with lap splicing of longitudinal reinforcement in the plastic hinge region, and to develop the enhancement scheme of their seismic capacity by retrofitting with glassfiber sheets and to develop appropriate limited ductility design concept in low or moderate seismicity region. Nine test specimens in the aspect ratio of 4.0 were made with three confinement ratios and three types of lap splicing. Quasi-static tests under three different axial load levees were conducted. It has been observed that displacement ductility ratios of test columns with lap splicing were significantly reduced.

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Identification of neoantigens derived from alternative splicing and RNA modification

  • Park, Jiyeon;Chung, Yeun-Jun
    • 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.

스플라이스식 와이어로프 슬링의 편입법에 따른 사용하중한계효율 (Work limit Load Efficiency According to Splicing Method for Hand Spliced Wirerope Sling)

  • 박재석;한경훈
    • 한국안전학회지
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    • 제25권6호
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    • pp.70-74
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    • 2010
  • For each strand of wirerope sling, the international standards, ISO-8794, EN-13414 specify that the splice shall have five series of load carrying tucks. At least three of the load carrying tucks shall be made with the whole strand. And, the breaking force of the splice shall not be less than 70% or 80% of that of rope. But, There are no prescriptions for splicing types against different efficiency of each splicing type being used many workplace. In this study, analysis the work limit load efficiency according to variation of number of tucks and splicing types by experimental method As a result, the number of tucks 3+2 had the highest breaking efficiency.

SR Proteins: Binders, Regulators, and Connectors of RNA

  • Jeong, Sunjoo
    • Molecules and Cells
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    • 제40권1호
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    • pp.1-9
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    • 2017
  • Serine and arginine-rich (SR) proteins are RNA-binding proteins (RBPs) known as constitutive and alternative splicing regulators. As splicing is linked to transcriptional and post-transcriptional steps, SR proteins are implicated in the regulation of multiple aspects of the gene expression program. Recent global analyses of SR-RNA interaction maps have advanced our understanding of SR-regulated gene expression. Diverse SR proteins play partially overlapping but distinct roles in transcription-coupled splicing and mRNA processing in the nucleus. In addition, shuttling SR proteins act as adaptors for mRNA export and as regulators for translation in the cytoplasm. This mini-review will summarize the roles of SR proteins as RNA binders, regulators, and connectors from transcription in the nucleus to translation in the cytoplasm.

HExDB: Human EXon DataBase for Alternative Splicing Pattern Analysis

  • Park, Junghwan;Lee, Minho;Bhak, Jong
    • Genomics & Informatics
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    • 제3권3호
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    • pp.80-85
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    • 2005
  • HExDB is a database for analyzing exon and splicing pattern information in Homo sapiens. HExDB is useful for specific purposes: 1) to design primers for exon amplification from cDNA and 2) to understand the change of ORFs by alternative splicing. HExDB was constructed by integrating data from AltExtron which is the computationally predicted exon database, Ensemble cDNA annotation, and Affymetrix genome tile published recently. Although it may contain false positive data, HExDB is good starting point due to its sensitivity. At present, there areas many as 2,046,519 exons stored in the HExDB. We found that $16.8\%$ of the exons in the database was constitutive exons and $83.1\%$ were novel gene exons.

광자결정 광섬유와 단일모드 광섬유 저손실 융착접속 (Low Loss Fusion Splicing of Photonic Crystal Fiber and Single-Mode Fiber)

  • 안진수;박광노;김길환;이상배;이경식
    • 대한전자공학회논문지SD
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    • 제46권7호
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    • pp.15-21
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    • 2009
  • 단일모드 광섬유(SMF)와 포토닉 밴드갭 광섬유(PBGF), SMF와 고비선형 광자결정 광섬유(NL-PCF)의 저손실 융착접속을 위한 방법을 제안하였다. SMF와 PBGF를 융착접속할 경우 PBGF의 공기구멍 붕괴현상에 의한 손실이 가장 큰 영향을 미치므로 PBGF의 공기구멍을 유지시키기 위해서 광섬유 융착접속기를 최적화하여 접속손실을 1.22 dB이하로 줄였다. SMF와 NL-PCF의 융착접속시에는 Ultra High Numerical Aperture(UHNA)광섬유를 두 광섬유 사이에 삽입하여 융착접속하는 방법을 적용하여 평균 2.59 dB이하로 접속손실을 줄였다.

광섬유 융착 부위 중접용 미소 직경 복합재료 스프링 구조물 개발 (A Development of Small-diameter Composite Helical Spring Structure for Reinforcement of Fiber Splice)

  • 윤영기;정승환;이우일;이병호;윤희석
    • Composites Research
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    • 제16권2호
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    • pp.26-32
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    • 2003
  • 레이저 융착된 광섬유의 절단 부위에 대한 보호를 위한 관심이 크게 높아지고 있다 일반적으로 절단된 광섬유의 융착부분은 다른 부위에 비해 상대적으로 매우 취약하며 이러한 이유로 광섬유를 광 통신망에 사용할 때 동일 부분에서의 손실이 추가적으로 일어날 수 있다 일반적으로 광섬유 융착 부위는 일반 광섬유의 파괴 강도에 비해 약 1/10인 0.4~l kg로 감소된다. 이러한 이유로 인해 광 융착 부위의 보강이 절실히 요구되고 있다. 그러나, 이러한 구조물의 대부분이 철심 형태의 구조물을 삽입한 슬리브로 보강됨에 따라 굽힘에 대해 효과적으로 대응하지 못할 뿐 아니라 일단 구조물이 굽혀졌을 경우에는 지속적인 광 손실을 발생시키는 요인이 된다. 이러한 문제점을 보완하기 위하여 복합재료로 제작된 코일형 스프링 구조물 형태의 슬리브가 제안되었다. 이러한 슬리브는 기존의 슬리브의 취약점이었던 직하중에 대해 서로 효과적으로 반응할 뿐 아니라 굽힘 및 인장/압축 하중에도 효과가 있음을 알 수 있었다.

Gain of New Exons and Promoters by Lineage-Specific Transposable Elements-Integration and Conservation Event on CHRM3 Gene

  • Huh, Jae-Won;Kim, Young-Hyun;Lee, Sang-Rae;Kim, Hyoungwoo;Kim, Dae-Soo;Kim, Heui-Soo;Kang, Han-Seok;Chang, Kyu-Tae
    • Molecules and Cells
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    • 제28권2호
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    • pp.111-117
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    • 2009
  • The CHRM3 gene is a member of the muscarinic acetylcholine receptor family that plays important roles in the regulation of fundamental physiological functions. The evolutionary mechanism of exon-acquisition and alternative splicing of the CHRM3 gene in relation to transposable elements (TEs) were analyzed using experimental approaches and in silico analysis. Five different transcript variants (T1, T2, T3, T3-1, and T4) derived from three distinct promoter regions (T1: L1HS, T2, T4: original, T3, T3-1: THE1C) were identified. A placenta (T1) and testis (T3 and T3-1)-dominated expression pattern appeared to be controlled by different TEs (L1HS and THE1C) that were integrated into the common ancestor genome during primate evolution. Remarkably, the T1 transcript was formed by the integration event of the human specific L1HS element. Among the 12 different brain regions, the brain stem, olfactory region, and cerebellum showed decreased expression patterns. Evolutionary analysis of splicing sites and alternative splicing suggested that the exon-acquisition event was determined by a selection and conservation mechanism. Furthermore, continuous integration events of transposable elements could produce lineage specific alternative transcripts by providing novel promoters and splicing sites. Taken together, exon-acquisition and alternative splicing events of CHRM3 genes were shown to have occurred through the continuous integration of transposable elements following conservation.