• Title/Summary/Keyword: RNA 1

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Longevity regulation by NMD-mediated mRNA quality control

  • Son, Heehwa G.;Lee, Seung-Jae V.
    • BMB Reports
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    • v.50 no.4
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    • pp.160-161
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    • 2017
  • Proper maintenance of biological components is crucial for longevity and healthy aging. Although the role of homeostatic maintenance systems for DNA and protein in longevity is established, it remains largely unknown for RNA. In our recent work, we show that nonsense-mediated mRNA decay (NMD) promotes longevity in the roundworm C. elegans by enhancing RNA quality control. We find that the activity of NMD decreases during aging, raising the possibility that RNA quality declines in old animals. We then show that key components of NMD complex are required for prolonged lifespan in C. elegans. In addition, animals with reduced insulin/insulin-like growth factor-1 (IGF-1) signaling (IIS), a representative longevity model, display increased NMD activity. Thus, up-regulation of NMD appears to play crucial roles in longevity conferred by reduced IIS via enhancing mRNA quality control. As both IIS and NMD pathways are evolutionarily conserved, mammals including humans may be equipped with similar RNA quality control systems to achieve longevity.

Prediction of protein binding regions in RNA using random forest (Random forest를 이용한 RNA에서의 단백질 결합 영역 예측)

  • Choi, Daesik;Park, Byungkyu;Chae, Hanju;Lee, Wook;Han, Kyungsook
    • Proceedings of the Korea Information Processing Society Conference
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    • 2016.10a
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    • pp.583-586
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    • 2016
  • 단백질과 RNA의 상호작용 데이터가 대량으로 늘어남에 따라, 단백질과 RNA의 결합부위를 예측하는 계산학적인 방법들이 많이 개발되고 있다. 하지만, 많은 계산학적인 방법들은 단백질에서 단백질과 RNA 결합부위를 예측한다는 한계점이 있었다. 본 논문에서는 RNA와 단백질의 서열정보를 모두 사용하여, 단백질과 결합하는 RNA 결합부위를 예측하는 기법과 그 결과를 논한다. WEKA random forest(http://www.cs.waikato.ac.nz/ml/weka/)를 이용하여 예측 모델을 개발하였고, RNA 서열의 서열 프로파일, 서열 composition, 결합 상대방의 단백질의 특성 등을 특정으로 표현하였다. Random forest 기법을 사용한 cross validation의 결과로서 1:1 모델에서 제일 높은 성능인 92.4% sensitivity, 92.0% specificity, 92.2% accuracy를 보였고, independent test에서는 72.5% sensitivity, 90.0% specificity, 2.1% accuracy를 보였다.

Effect of Tex1/THOC3, a component of THO complex, on growth and mRNA export in fission yeast (분열효모에서 THO 복합체의 구성요소인 Tex1/THOC3가 생장 및 mRNA 방출에 미치는 영향)

  • Bae, Soo Jeong;Koh, Eun-Jin;Yoon, Jin Ho
    • Korean Journal of Microbiology
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    • v.53 no.4
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    • pp.292-296
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    • 2017
  • In eukaryote, THO/TREX complex plays a critical role in transcriptional elongation, pre-mRNA processing, and nuclear mRNA export. This complex is evolutionally well- conserved, but there are some differences in composition and function according to organisms. Here we showed that spTex1, a component of THO/TREX complex, is not essential for growth and mRNA export in a fission yeast, Schizosaccharomyces pombe, which is more similar to higher eukaryote than budding yeast. Deletion and overexpression of the spTex1 gene do not lead to any detectable growth phenotype and accumulation of poly(A)+ RNA in the nucleus. And the spTex1-GFP protein is localized mainly in the nucleus. Yeast two-hybrid and Co-immunoprecipitation analysis showed that the spTex1 protein interacted with spHpr1 (THOC1) and spTho2 (THOC2), main subunits of THO complex. We conclude that the S. pombe Tex1 is a component of THO/TREX complex, but does not plays important roles in growth and bulk mRNA export from the nucleus.

미토콘드리아의 $tRNA^{Asp}$ 유전자의 한 돌연변이와 그의 억제 유전자들

  • 강영원
    • The Microorganisms and Industry
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    • v.17 no.1
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    • pp.19-24
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    • 1991
  • tRNA는 그 생화학적인 역할이 잘 알려져 있고 구조적으로 안정하며, 이용할 수 있는 분자 생물학적인 자료가 많아, 유전자 발현과 유전자 산물간의 조직적인 상호작용을 연구하는데 적합한 재료이다. 효모의 미토콘드리아에는 24개의 tRNA 유전자가 잇어, 단백질 합성에 필요한 tRNA를 자급하고 있으나, 유전자 발현과 processing에 관여하는 모든 정보가, tRNA의 5' 부위를 process하는데 관여하는 효소중 RNA subunit인 9S RNA를 산출하는 tsl 유전자를 제외하고, 핵 유전자에 존재한다. 효모의 대표적인 종인 Saccharomyces cerevisiae의 $tRNA^{Asp}$ 유전자에 결함이 생긴 한 돌연변이 균주의 성질을 조사하고, 억제현상(suppression)을 규명하므로써 tRNA의 구조적 특성을 파악하고, 나아가 미토콘드리아 생성에 관여하는 핵 유전자를 찾아보고자 한다.

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Effects of 3-methylcholanthrene on the Expression of Drug Metabolizing Enzyme Genes in Monkey Brain (원숭이 뇌 약물대사효소 유전자 발현에 미치는 3-methylcholanthrene 영향)

  • 이경원;아사오카;신윤용
    • Environmental Mutagens and Carcinogens
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    • v.24 no.1
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    • pp.40-45
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    • 2004
  • In order to understand the mechanism of the regulation of drug metabolizing enzyme gene expression, we have studied the induction of CYP1A1 and GSTα, μ, π enzymes in Japanese monkey and rhesus monkey after the treatment with 3-methylcholanthrene (3MC) and di-n- butyl phthalate (DBP) and bisphenol A (BPA). The levels of mRNA were measured_by RT-PCR in brain, intestine and liver. In the case of adult monkey, treatment with 3MC induced CYP1A1 mRNA in brain by 2-fold. The treatment with DBP induced CYP1A1 mRNA. Effects of 3MC and DBP on GST mRNA expression was not clear. But GSTμ was slightly inhibited by the treatment with 3MC and DBP. GSTα was not induced by the treatment with 3MC and DBP in brain. GSTπ was slightly induced by the treatment with 3MC and DBP in brain. In the case of fetus monkey, the basal levels of fetus CYP1A1 mRNA and GSTs mRNA were relatively low compared to adult monkey. As the age of monkey increased, the basal levels of CYP1A1 mRNA were also increased. 3MC induced the expression of CYP1A1 mRNA in liver, whereas it didn't significantly induce CYP1A1 mRNA in brain. The levels of GSTμ and GSTα were not changed by the treatment with 3MC and DBP. GSTπ was slightly induced by the treatment with 3MC and DBP.

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Effects of 3-methylcholanthrene on the Expression of Drug Metabolizing Enzyme Genes in Monkey Intestine (원숭이 소장 약물대사효소 유전자 발현에 미치는 3-methylcholanthrene 영향)

  • 이경원;아사오카;신윤용
    • Environmental Mutagens and Carcinogens
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    • v.24 no.1
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    • pp.19-24
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    • 2004
  • In order to understand the mechanism of the regulation of drug metabolizing enzyme gene expression, we have studied the induction of CYP1A1 and $GST\alpha,$ $\mu,$ $\pi$ enzymes in Japanese monkey and rhesus monkey after the treatment with 3-methylcholanthrene (3MC) and di-n-butyl phthalate (DBP) and bisphenol A (BPA). The levels of mRNA were measured by RT-PCR in brain, intestine and liver. In the case of adult monkey, treatment with 3MC induced CYP1A1 mRNA in intestine by 11-fold. The treatment with DBP induced CYP1A1 mRNA. Effects of 3MC and DBP on GST mRNA expression was not clear. But $GST\mu$ was slightly inhibited by the treatment with 3MC and DBP. $GST\alpha$ was induced in intestine by 1.5-fold. $GST\pi$ was slightly induced by the treatment with 3MC and DBP in intestine. In the case of fetus monkey, the basal levels of fetus CYP1A1 mRNA and GSTs mRNA were relatively low compared to adult monkey. As the age of monkey increased, the basal levels of CYP1A1 mRNA were also increased. 3MC induced the expression of CYP1A1 mRNA didn't significantly induce CYP1A1 mRNA in intestine. The levels of $GST\mu$ and $GST\pi$ were not changed by the treatment with 3MC and DBP. $GST\pi$ was slightly induced by the treatment with 3MC and DBP.

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A new function of glucocorticoid receptor: regulation of mRNA stability

  • Park, Ok Hyun;Do, Eunjin;Kim, Yoon Ki
    • BMB Reports
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    • v.48 no.7
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    • pp.367-368
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    • 2015
  • It has long been thought that glucocorticoid receptor (GR) functions as a DNA-binding transcription factor in response to its ligand (a glucocorticoid) and thus regulates various cellular and physiological processes. It is also known that GR can bind not only to DNA but also to mRNA; this observation points to the possible role of GR in mRNA metabolism. Recent data revealed a molecular mechanism by which binding of GR to target mRNA elicits rapid mRNA degradation. GR binds to specific RNA sequences regardless of the presence of a ligand. In the presence of a ligand, however, the mRNA-associated GR can recruit PNRC2 and UPF1, both of which are specific factors involved in nonsense-mediated mRNA decay (NMD). PNRC2 then recruits the decapping complex, consequently promoting mRNA degradation. This mode of mRNA decay is termed "GR-mediated mRNA decay" (GMD). Further research demonstrated that GMD plays a critical role in chemotaxis of immune cells by targeting CCL2 mRNA. All these observations provide molecular insights into a previously unappreciated function of GR in posttranscriptional regulation of gene expression. [BMB Reports 2015; 48(7): 367-368]

Autocrine Regulation of Gonadotropin-releasing Hormone (GnRH) Operates at Multiple Control levels of GnRH Gene Expression in GT1-1 Neuronal Cells

  • Jin Han;Sehyung Cho;Woong Sun;Kyungjin Kim
    • Animal cells and systems
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    • v.2 no.4
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    • pp.483-488
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    • 1998
  • We previously found that a potent gonadotropin-releasing hormone (GnRH) agonist, buserelin, decreases GnRH promoter activity together with GnRH mRNA level, providing evidence for an autoregulatory mechanism operating at the level of GnRH gene transcription in immortalized GT1-1 neuronal cells. To examine whether agonist-induced decrease in GnRH mRNA level requires the continuous presence of buserelin, we performed a pulse-chase experiment of buserelin treatment. Short-term exposure (15 min) of GT1-1 neuronal cells to buserelin ($10{\mu}M$) was able to decrease GnRH mRNA levels when determined 24 h later. When GT1-1 cells were treated with buserelin ( $10{\mu}M$) for 30 min and then incubated for 1, 3, 6, 12, 24, and 48 h after buserelin removal, a significant decrease in GnRH mRNA levels was observed after the 12 h incubation period. These data indicate that inhibitory signaling upon buserelin treatment may occur rapidly, but requires a long time (at least 12 h) to significantly decrease the GnRH mRNA level. To examine the possible involvement of de novo synthesis and/or mRNA stability in buserelin-induced decrease in GnRH gene expression, actinomycin D ($5{\mu}m/ml$), a potent RNA synthesis blocker, was co-treated with buserelin. Actinomycin D alone failed to alter basal GnRH mRNA Revel, but blocked the buserelin-induced decrease in GnRH mRNA level at 12 h of post-treatment. These data suggest that buserelin may exert its inhibitory action by altering the stability of GnRH mRNA. Moreover, a polvsomal RNA separation by sucrose gradient centrifugation demonstrated that buserelin decreased the translational efficiency of the transcribed GnRH mRNA. Taken together, these results clearly indicate that GnRH agonist buserelin acts as an inhibitory signal at multiple levels such as transcription mRNA stability, and translation.

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THE EFFECT OF XYLITOL ON THE EXPRESSION OF GTF GENE (gtf 유전자 발현에 대한 xylitol의 영향)

  • Yeom, Chung-Hyun;Chung, Jin;Jeong, Tae-Sung;Kim, Shin
    • Journal of the korean academy of Pediatric Dentistry
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    • v.31 no.2
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    • pp.304-313
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    • 2004
  • Xylitol, a five-carbon natural sugar alcohol, is widely used non-cariogenic sugar substitute. In present study, the effects of xylitol on the expression of mRNA for glucosyltransferase which synthesizes glucan from sucrose were detected by Fluorescent in situ hybridization (FISH) and flow cytometry. FITC fluorescences for mRNA of gtfB, gtfC and gtfD were decreased further with increasing concentration of xylitol from 1% to 10% when detected by FISH. Flow cytometric analysis also showed that the expression of gtfB, gtfC and gtfD was increased by the addition of sucrose and decreased by the addition of xylitol to BHI broth containing 1% sucrose. In conclusion, the expression of gtfB, gtfC and gtfD mRNA was decreased by the addition of xylitol.

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Evolutionary Optimization of Models for Mature microRNA Prediction (Mature microRNA 위치 예측 모델의 진화적 최적화)

  • Kim Jin-Han;Nam Jin-Wu;Zhang Byoung-Tak
    • Proceedings of the Korean Information Science Society Conference
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    • 2006.06a
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    • pp.67-69
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    • 2006
  • MicroRNA (miRNA)는 생체내에서 gene regulation에 관여하는 핵심 small RNA 중 하나이다. miRNA는 Primary miRNA, Precursor miRNA, mature miRNA의 과정으로 processing 된다. miRNA 최종 형태인 mature miRNA의 정확한 위치 예측은 miRNA 예측의 필수적인 부분이다. 본 논문에서는, 진화적 최적화 예측 모델 중 하나인 유전 알고리즘을 이용하여 mature miRNA의 정확한 위치 예측을 수행한다. 제시된 방법은 이미 알려진 mature miRNA 위치를 positive example로 하고 임의로 생성한 위치를 negative example로 하여 서로의 linear scoring function 적합성 함수의 값 차이가 최대한으로 되도록 예측 모델을 진화시킨다. 유전 알고리즘을 이용한 진화적 최적화 모델로부터 mature miRNA 위치 예측에서 약 1.7nt 오차를 보여 기존의 방법 보다 개선된 성능을 보인다.

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