• 제목/요약/키워드: Rearrangements

검색결과 118건 처리시간 0.024초

The Dharma of Nonsense-Mediated mRNA Decay in Mammalian Cells

  • Popp, Maximilian Wei-Lin;Maquat, Lynne E.
    • Molecules and Cells
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    • 제37권1호
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    • pp.1-8
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    • 2014
  • Mammalian-cell messenger RNAs (mRNAs) are generated in the nucleus from precursor RNAs (pre-mRNAs, which often contain one or more introns) that are complexed with an array of incompletely inventoried proteins. During their biogenesis, pre-mRNAs and their derivative mRNAs are subject to extensive cis-modifications. These modifications promote the binding of distinct polypeptides that mediate a diverse array of functions needed for mRNA metabolism, including nuclear export, inspection by the nonsense-mediated mRNA decay (NMD) quality-control machinery, and synthesis of the encoded protein product. Ribonucleoprotein complex (RNP) remodeling through the loss and gain of protein constituents before and after pre-mRNA splicing, during mRNA export, and within the cytoplasm facilitates NMD, ensuring integrity of the transcriptome. Here we review the mRNP rearrangements that culminate in detection and elimination of faulty transcripts by mammalian-cell NMD.

Prenatal diagnosis of 4p deletion syndrome: A case series report

  • Kwak, Dong Wook;Ahn, Hyun Kyong
    • Journal of Genetic Medicine
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    • 제14권1호
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    • pp.38-42
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    • 2017
  • The 4p deletion syndrome, also known as Wolf-Hirschhorn syndrome, is a well-known genetic disorder caused by a partial deletion of the short arm of chromosome 4. The great variability in the extent of the 4p deletion and the possible contribution of additional genetic rearrangements leads to a wide spectrum of clinical manifestations. Herein, we present our experience with eight cases of 4p deletion syndrome, ascertained prenatally between 1998 and 2016 at our hospital.

Beckmann Rearrangements of 1-Indanone Oxime Derivatives Using Aluminum Chloride and Mechanistic Considerations

  • 이병세;추소영;이인영;이본수;송중의;지대윤
    • Bulletin of the Korean Chemical Society
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    • 제21권9호
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    • pp.860-866
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    • 2000
  • Hydrocarbostyril, which is a key intermediate in our new synthetic route to 6-nitroquipazine, can be prepared from 1-indanone oxime by Beckmann rearrangement. We have optimized the reaction by using a Lewis acid, aluminum chloride,in the yield of 91% instead of common acids such as polyphosphoric acid,and sulfuric acid used in conventional Beckmann rearrangement (20% in the literature, 10% in our experiment).The optimized condition is established by usingthree equivalents of aluminum chloride in CH2Cl2 at -40 $^{\circ}C$ - room tempera-turefor 40 min. We have applied this condition to other 1-indanone derivatives, such as 4-methyl-, 4-methoxy-, 4-nitro and 6-nitro-1-indanones. The mechanism ofthis BR has been proposed on the basis of the effect of tem-perature and substituenton product ratio, with the aid of PM3 calculation for a model system.

Preparation of Enantiomerically Pure Chiral builing block ((E)-4-(tributylstannanyl) but-3-en-2-ol) via lipase-mediated resolution

  • Lee, Tae-Ho;Ko, Hyo-Jin;Lee, Hye-Seung;Kim, Sang-Hee
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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    • pp.179.1-179.1
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    • 2003
  • Chiral building blocks have the importance in the pharmaceutical and agrochemical industries as well as in the development of rapid and efficient syntheses of bioactive compounds and natural product. Vinylstannane contains two synthetically useful functional groups (vinylstannane and allylic alcohol). The vinylstannane functional group can be used in C-C bond formation under a variety of conditions and the allylic alcohol functional can be used in hydroxyl-directed epoxidations, cyclopropanations, and sigmatropic rearrangements. (omitted)

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예후가 좋지 않은 갑상선암에 대한 최신 치료 방침 (Recent Improvements in the Treatment of High-Risk Thyroid Cancer)

  • 이은경
    • 대한두경부종양학회지
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    • 제38권1호
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    • pp.1-9
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    • 2022
  • Thyroid cancer is one of the slow-growing tumors with excellent oncological outcomes. However, a small set of patients with unexpectedly severe outcomes are usually ignored. Anaplastic thyroid cancer (ATC) remains one of the most aggressive and lethal solid tumors. Recently, dabrafenib and trametinib combination therapy or neoadjuvant BRAF induction therapy has shown promising results. In addition, a combination of targeted drugs, immunotherapy, surgery, and radiation therapy can improve overall survival in ATC patients. Another disease for which there is no breakthrough treatment is radioactive iodine-refractory differentiated thyroid cancer (DTC). To date, multikinase inhibitors (sorafenib, lenvatinib) targeting the growth factor signaling pathway have been developed and approved as anticancer agents for patients with advanced DTC. This review includes results from multikinase inhibitors to the emergence of new target molecules, including rearrangements during transformation (RET) and tropomyosin receptor kinase (TRK).

백혈병 미세잔존질환 정량검출을 위한 실시간 역전사중합효소연쇄반응법의 유용성 (Utility of Real Time RT-PCR for the Quantitative Detection of Minimal Residual Disease in Hematological Malignancy)

  • 조정애;김다운;정성두;천지선;나경아;김혜란;김진각;김인환;김수현;신명근;김형록
    • 대한임상검사과학회지
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    • 제41권1호
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    • pp.11-23
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    • 2009
  • Chromosomal rearrangements are major pathology in hematological malignancies. The detection of minimal residual disease (MRD) for these gene rearrangements helps in monitoring treatment outcomes and predicting prognosis of patients. Recently, quantification of these gene transcripts based on real-time quantitative polymerase chain reaction (RQ-PCR) has been used as MRD detection. The purpose of this study is to ensure the usefulness of the RQ-PCR technique for detecting MRD in hamatological malignancy patients. The patients had been diagnosed to AML1-ETO positive AML, PML-RARa positive AML and BCR-ABL positive MPN at Chonnam National University Hwasun Hospital from Jan. 2006 to Aug. 2008. The fusion transcript was quntified by RQ-PCR and analyzed in comparison to conventional cytogenetics, FISH and RT-PCR. The fusion gene transcript was quantified by RQ-PCR in 57 samples from 14 patients with AML1-ETO positive AML, 79 samples from 27 patients with PML-RARa positive AML and 108 samples from 36 patients with CML. At diagnosis, the quantitative fusion transcripts for AM1-ETO, PML-RARa and BCR-ABL showed the range of 0.485552651~10.82233683 (mean 3.782217131, SD 2.998052348), 0.005300395~0.29267494 (mean 0.056901315, SD 0.080131381) and 0.1293929~12.94826849 (mean 1.701935665, SD 2.200913158). The increase of AML1-ETO fusion gene transcripts preceded morphologic relapse in two patients. Quantification of fusion gene transcripts by RQ-PCR could detected MRD in samples which were negative by in cytogenetic analysis or FISH. Our findings indicated that quantitative analysis of AML1-ETO, PML-RARa and BCR-ABL transcripts by RQ-PCR might be a useful tool for the monitoring of minimal residual disease in hematological malignancies.

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3중 DNA probe를 이용한 FISH(fluorescence in situ hybridization) 기법으로 방사선에 의한 염색체 이상 분석 (Analysis of Chromosome aberrations by fluorescence in situ hybridization using triple chromosome-specific probes in human lymphocyte exposed to radiation)

  • 정해원;김수영;하성환
    • Journal of Radiation Protection and Research
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    • 제24권1호
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    • pp.45-53
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    • 1999
  • 각 염색체에 특이한 DNA probe를 이용하는 FISH기법은 방사선에 의해 유발된 상호전좌 및 삽입 등의 염색체의 구조적 변화를 측정하는 매우 효과적인 방법으로서 그 활용성이 증가되고 있다. 본연구는 방사선 피폭시 생물학적 선량측정법으로서 FISH기법을 활용하기 위하여 사람의 1, 2, 4번 염색체에 특이한 probe를 이용하여 고선량 단일 피폭시 유발된 각종 염색체 이상빈도를 관찰하고 이를 PAINT분류체계에 의해 분석하였다. 방사선 조사에 의한 염색체 이상빈도는 상호전좌(t)와 이동원염색체(dic)의 수가 선량 증가에 따라 같이 증가하는 것을 알 수 있으며 color junction의 수도 선량에 따라 증가하는 것을 알 수 있었다. 상호전좌의 빈도는 이동원 염색체의 빈도보다 상대적으로 높게 나타났다. 삽입(ins), 무동원염색체(ace), 및 환상염색체(r)의 수도 선량 증가에 따라 같이 증가하는 것을 알 수 있었다. 기존의 염색체재배열 분석방법과 비교해 볼 때 FISH기법은 다양한 형태의 염색체재해열을 보다 쉽게 관찰할 수 있게 하며 생물학적 선량제로서 중요한 역할을 할 것이라 기대된다.

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Chimeric RNAs as potential biomarkers for tumor diagnosis

  • Zhou, Jianhua;Liao, Joshua;Zheng, Xuexiu;Shen, Haihong
    • BMB Reports
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    • 제45권3호
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    • pp.133-140
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    • 2012
  • Cancers claim millions of lives each year. Early detection that can enable a higher chance of cure is of paramount importance to cancer patients. However, diagnostic tools for many forms of tumors have been lacking. Over the last few years, studies of chimeric RNAs as biomarkers have emerged. Numerous reports using bioinformatics and screening methodologies have described more than 30,000 expressed sequence tags (EST) or cDNA sequences as putative chimeric RNAs. While cancer cells have been well known to contain fusion genes derived from chromosomal translocations, rearrangements or deletions, recent studies suggest that trans-splicing in cells may be another source of chimeric RNA production. Unlike cis-splicing, trans-splicing takes place between two pre-mRNA molecules, which are in most cases derived from two different genes, generating a chimeric non-co-linear RNA. It is possible that trans-splicing occurs in normal cells at high frequencies but the resulting chimeric RNAs exist only at low levels. However the levels of certain RNA chimeras may be elevated in cancers, leading to the formation of fusion genes. In light of the fact that chimeric RNAs have been shown to be overrepresented in various tumors, studies of the mechanisms that produce chimeric RNAs and identification of signature RNA chimeras as biomarkers present an opportunity for the development of diagnoses for early tumor detection.

정준 상관 분석을 이용한 잡음 섞인 음성 신호의 분리 (Segaration of Corrupted Speech Signals using Canonical Correlation Analysis)

  • 김선일
    • 한국정보통신학회:학술대회논문집
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    • 한국정보통신학회 2012년도 춘계학술대회
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    • pp.164-167
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    • 2012
  • 음성 신호와 함께 섞인 자동차 배기 소음을 서로 분리해 내는 기술은 점점 음성을 중심으로 발전해가는 인터페이스를 현실화하는데 실질적으로 필요한 기술이다. 따라서 자동차 배기음이 섞인 음성신호를 두 신호간의 독립성이 보장되지 않고 두 신호에 대한 사전 정보가 없는 상태에서 분리해 내기 위해 정준 상관 분석을 사용하여 두 신호를 분리해 내는 연구를 진행하였다. 정준 상관 분석을 이용하여 음성을 분리해 내기 위해서는 분석에 쓰이는 신호의 구성이 중요하다. 정준 상관 분석에 대해 알아보고 음성과 자동차 배기 소음이 섞인 두 개의 신호를 받아서 이를 재구성하여 정준 상관분석을 이용하여 자동차 소음과 음성을 분리해 내었다. Blind Source Separation에 쓰이는 다른 방법과 비교했을 때 독립성이 보장되지 않는 신호에 대해서도 분리가 가능하므로 응용 대상이 상대적으로 넓어 실용적 응용이 가능하다고 할 수 있다.

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Evidence for VH Gene Replacement in Human Fetal B Cells

  • Lee, Jisoo;Cho, Young Joo;Lipsky, Peter E.
    • IMMUNE NETWORK
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    • 제2권2호
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    • pp.79-85
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    • 2002
  • Background: In contrast to evidences of Ig H chain receptor editing in transformed cell lines and transgenic mouse models, there has been no direct evidence that this phenomenon occurs in human developing B cells. Methods: $V_HDJ_H$ rearrangements were obtained from genomic DNA of individual $IgM^-$ B cells from liver and $IgM^+B$ cells from bone marrow of 18 wk of gestation human fetus by PCR amplification and direct sequencing. Results: We found three examples of H chain receptor editing from $IgM^+$ and $IgM^-human$ fetal B cells. Two types of $V_H$ replacements were identified. The first involved $V_H$ hybrid formation, in which part of a $V_H$ gene from the initial VDJ rearrangement is replaced by part of an upstream $V_H$ gene at the site of cryptic RSS. The second involved a gene conversion like replacement of CDR2, in which another $V_H$ gene donated a portion of its CDR2 sequence to the initial VDJ rearrangement. Conclusion: These data provide evidence of receptor editing at the H chain loci in developing human B cells, and also the first evidence of a gene conversion event in human Ig genes.