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Cell 35건

  1. [해외논문]   Brain-wide Electrical Spatiotemporal Dynamics Encode Depression Vulnerability  

    Hultman, Rainbo , Ulrich, Kyle , Sachs, Benjamin D. , Blount, Cameron , Carlson, David E. , Ndubuizu, Nkemdilim , Bagot, Rosemary C. , Parise, Eric M. , Vu, Mai-Anh T. , Gallagher, Neil M. , Wang, Joyce , Silva, Alcino J. , Deisseroth, Karl , Mague, Stephen D. , Caron, Marc G. , Nestler, Eric J. , Carin, Lawrence , Dzirasa, Kafui
    Cell v.173 no.1 ,pp. 166 - 180.e14 , 2018 , 0092-8674 ,

    초록

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  2. [해외논문]   Brain-wide Electrical Spatiotemporal Dynamics Encode Depression Vulnerability   SCI SCIE

    Hultman, Rainbo (Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA ) , Ulrich, Kyle (Department of Electrical and Computer Engineering, Duke University, Durham, NC 22208, USA ) , Sachs, Benjamin D. (Department of Psychological and Brain Sciences, Villanova University, Villanova, PA, 19085, USA ) , Blount, Cameron (Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA ) , Carlson, David E. (Department of Civil and Electrical Engineering, Biostatistics and Bioinformatics, Duke University, Durham, NC 22208, USA ) , Ndubuizu, Nkemdilim (Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA ) , Bagot, Rosemary C. (Fishberg, Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA ) , Parise, Eric M. (Fishberg, Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA ) , Vu, Mai-Anh T. (Department of Psychiatry and Behavioral Sciences, Duke Un) , Gallagher, Neil M. , Wang, Joyce , Silva, Alcino J. , Deisseroth, Karl , Mague, Stephen D. , Caron, Marc G. , Nestler, Eric J. , Carin, Lawrence , Dzirasa, Kafui
    Cell v.173 no.1 ,pp. 166 - 180.e14 , 2018 , 0092-8674 ,

    초록

    Summary Brain-wide fluctuations in local field potential oscillations reflect emergent network-level signals that mediate behavior. Cracking the code whereby these oscillations coordinate in time and space (spatiotemporal dynamics) to represent complex behaviors would provide fundamental insights into how the brain signals emotional pathology. Using machine learning, we discover a spatiotemporal dynamic network that predicts the emergence of major depressive disorder (MDD)-related behavioral dysfunction in mice subjected to chronic social defeat stress. Activity patterns in this network originate in prefrontal cortex and ventral striatum, relay through amygdala and ventral tegmental area, and converge in ventral hippocampus. This network is increased by acute threat, and it is also enhanced in three independent models of MDD vulnerability. Finally, we demonstrate that this vulnerability network is biologically distinct from the networks that encode dysfunction after stress. Thus, these findings reveal a convergent mechanism through which MDD vulnerability is mediated in the brain. Highlights Brain-wide electrical spatiotemporal dynamic map of stress states Hippocampally directed network signals stress vulnerability in stress-naive animals Early life stress increases activity in stress vulnerability network Stress vulnerability network is mechanistically distinct from pathology networks Graphical Abstract [DISPLAY OMISSION]

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  3. [해외논문]   Pervasive Regulatory Functions of mRNA Structure Revealed by High-Resolution SHAPE Probing  

    Mustoe, Anthony M. , Busan, Steven , Rice, Greggory M. , Hajdin, Christine E. , Peterson, Brant K. , Ruda, Vera M. , Kubica, Neil , Nutiu, Razvan , Baryza, Jeremy L. , Weeks, Kevin M.
    Cell v.173 no.1 ,pp. 181 - 195.e18 , 2018 , 0092-8674 ,

    초록

    Summary Brain-wide fluctuations in local field potential oscillations reflect emergent network-level signals that mediate behavior. Cracking the code whereby these oscillations coordinate in time and space (spatiotemporal dynamics) to represent complex behaviors would provide fundamental insights into how the brain signals emotional pathology. Using machine learning, we discover a spatiotemporal dynamic network that predicts the emergence of major depressive disorder (MDD)-related behavioral dysfunction in mice subjected to chronic social defeat stress. Activity patterns in this network originate in prefrontal cortex and ventral striatum, relay through amygdala and ventral tegmental area, and converge in ventral hippocampus. This network is increased by acute threat, and it is also enhanced in three independent models of MDD vulnerability. Finally, we demonstrate that this vulnerability network is biologically distinct from the networks that encode dysfunction after stress. Thus, these findings reveal a convergent mechanism through which MDD vulnerability is mediated in the brain. Highlights Brain-wide electrical spatiotemporal dynamic map of stress states Hippocampally directed network signals stress vulnerability in stress-naive animals Early life stress increases activity in stress vulnerability network Stress vulnerability network is mechanistically distinct from pathology networks Graphical Abstract [DISPLAY OMISSION]

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  4. [해외논문]   Pervasive Regulatory Functions of mRNA Structure Revealed by High-Resolution SHAPE Probing   SCI SCIE

    Mustoe, Anthony M. (Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA ) , Busan, Steven (Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA ) , Rice, Greggory M. (Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA ) , Hajdin, Christine E. (Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA ) , Peterson, Brant K. (Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA ) , Ruda, Vera M. (Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA ) , Kubica, Neil (Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA ) , Nutiu, Razvan (Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA ) , Baryza, Jeremy L. (Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA ) , Weeks, Kevin M. (Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA)
    Cell v.173 no.1 ,pp. 181 - 195.e18 , 2018 , 0092-8674 ,

    초록

    Summary mRNAs can fold into complex structures that regulate gene expression. Resolving such structures de novo has remained challenging and has limited our understanding of the prevalence and functions of mRNA structure. We use SHAPE-MaP experiments in living E. coli cells to derive quantitative, nucleotide-resolution structure models for 194 endogenous transcripts encompassing approximately 400 genes. Individual mRNAs have exceptionally diverse architectures, and most contain well-defined structures. Active translation destabilizes mRNA structure in cells. Nevertheless, mRNA structure remains similar between in-cell and cell-free environments, indicating broad potential for structure-mediated gene regulation. We find that the translation efficiency of endogenous genes is regulated by unfolding kinetics of structures overlapping the ribosome binding site. We discover conserved structured elements in 35% of UTRs, several of which we validate as novel protein binding motifs. RNA structure regulates every gene studied here in a meaningful way, implying that most functional structures remain to be discovered. Highlights E. coli mRNAs adopt highly diverse and complex structures Translation is the main source of mRNA structural destabilization in cells Translation efficiency is strongly correlated with ribosome-binding-site structure Conserved structured elements found in 35% of UTRs Graphical Abstract [DISPLAY OMISSION]

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    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  5. [해외논문]   Regulated Stochasticity in a Bacterial Signaling Network Permits Tolerance to a Rapid Environmental Change   SCI SCIE

    Carey, Jeffrey N. (Graduate Group in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA ) , Mettert, Erin L. (Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA ) , Roggiani, Manuela (Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA ) , Myers, Kevin S. (Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA ) , Kiley, Patricia J. (Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA ) , Goulian, Mark (Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA)
    Cell v.173 no.1 ,pp. 196 - 207.e14 , 2018 , 0092-8674 ,

    초록

    Summary Microbial populations can maximize fitness in dynamic environments through bet hedging, a process wherein a subpopulation assumes a phenotype not optimally adapted to the present environment but well adapted to an environment likely to be encountered. Here, we show that oxygen induces fluctuating expression of the trimethylamine oxide (TMAO) respiratory system of Escherichia coli , diversifying the cell population and enabling a bet-hedging strategy that permits growth following oxygen loss. This regulation by oxygen affects the variance in gene expression but leaves the mean unchanged. We show that the oxygen-sensitive transcription factor IscR is the key regulator of variability. Oxygen causes IscR to repress expression of a TMAO-responsive signaling system, allowing stochastic effects to have a strong effect on the output of the system and resulting in heterogeneous expression of the TMAO reduction machinery. This work reveals a mechanism through which cells regulate molecular noise to enhance fitness. Highlights Variance in TMAO reductase ( torCAD ) expression allows bet hedging on oxygen loss Oxygen-dependent repression of TMAO signaling genes regulates torCAD variance A point mutation in the repressor binding site derepresses TMAO signaling genes In the mutant, torCAD is uniformly expressed and bet hedging does not occur Graphical Abstract [DISPLAY OMISSION]

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  6. [해외논문]   Transposase-DNA Complex Structures Reveal Mechanisms for Conjugative Transposition of Antibiotic Resistance   SCI SCIE

    Rubio-Cosials, Anna (Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany ) , Schulz, Eike C. (Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany ) , Lambertsen, Lotte (Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany ) , Smyshlyaev, Georgy (Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany ) , Rojas-Cordova, Carlos (Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany ) , Forslund, Kristoffer (Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany ) , Karaca, Ezgi (Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany ) , Bebel, Aleksandra (Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany ) , Bork, Peer (Structural and Computational Biology Unit, European Molecular Bi) , Barabas, Orsolya
    Cell v.173 no.1 ,pp. 208 - 220.e20 , 2018 , 0092-8674 ,

    초록

    Summary Conjugative transposition drives the emergence of multidrug resistance in diverse bacterial pathogens, yet the mechanisms are poorly characterized. The Tn 1549 conjugative transposon propagates resistance to the antibiotic vancomycin used for severe drug-resistant infections. Here, we present four high-resolution structures of the conserved Y-transposase of Tn 1549 complexed with circular transposon DNA intermediates. The structures reveal individual transposition steps and explain how specific DNA distortion and cleavage mechanisms enable DNA strand exchange with an absolute minimum homology requirement. This appears to uniquely allow Tn 916 -like conjugative transposons to bypass DNA homology and insert into diverse genomic sites, expanding gene transfer. We further uncover a structural regulatory mechanism that prevents premature cleavage of the transposon DNA before a suitable target DNA is found and generate a peptide antagonist that interferes with the transposase-DNA structure to block transposition. Our results reveal mechanistic principles of conjugative transposition that could help control the spread of antibiotic resistance genes. Highlights Antibiotic resistance-carrying conjugative transposon integrase structure revealed DNA distortion and special cleavage site allow insertion into diverse genomic sites Key structural features are conserved among numerous conjugative transposons Structures uncover auto-inhibition, allowing transposition antagonist design Graphical Abstract [DISPLAY OMISSION]

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  7. [해외논문]   DNA Conformation Induces Adaptable Binding by Tandem Zinc Finger Proteins   SCI SCIE

    Patel, Anamika (Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA ) , Yang, Peng (The Eunice Kennedy Shriver National Institutes of Child Health and Human Development, NIH, Bethesda, MD 20892, USA ) , Tinkham, Matthew (The Eunice Kennedy Shriver National Institutes of Child Health and Human Development, NIH, Bethesda, MD 20892, USA ) , Pradhan, Mihika (Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA ) , Sun, Ming-An (The Eunice Kennedy Shriver National Institutes of Child Health and Human Development, NIH, Bethesda, MD 20892, USA ) , Wang, Yixuan (The Eunice Kennedy Shriver National Institutes of Child Health and Human Development, NIH, Bethesda, MD 20892, USA ) , Hoang, Don (The Eunice Kennedy Shriver National Institutes of Child Health and Human Development, NIH, Bethesda, MD 20892, USA ) , Wolf, Gernot (The Eunice Kennedy Shriver National Institutes of Child Health and Human Development, NIH, Bethesda, MD 20892, USA ) , Horton, John R. (Department of Molecular and Cellular Oncology, The University of Texas MD Anders) , Zhang, Xing , Macfarlan, Todd , Cheng, Xiaodong
    Cell v.173 no.1 ,pp. 221 - 233.e12 , 2018 , 0092-8674 ,

    초록

    Summary Tandem zinc finger (ZF) proteins are the largest and most rapidly diverging family of DNA-binding transcription regulators in mammals. ZFP568 represses a transcript of placental-specific insulin like growth factor 2 ( Igf2 -P0) in mice. ZFP568 binds a 24-base pair sequence-specific element upstream of Igf2 -P0 via the eleven-ZF array. Both DNA and protein conformations deviate from the conventional one finger-three bases recognition, with individual ZFs contacting 2, 3, or 4 bases and recognizing thymine on the opposite strand. These interactions arise from a shortened minor groove caused by an AT-rich stretch, suggesting adaptability of ZF arrays to sequence variations. Despite conservation in mammals, mutations at Igf2 and ZFP568 reduce their binding affinity in chimpanzee and humans. Our studies provide important insights into the evolutionary and structural dynamics of ZF-DNA interactions that play a key role in mammalian development and evolution. Highlights ZFP568 and its Igf2 -P0 binding activity is conserved in eutheria Mouse ZFP568 11-finger array makes numerous non-canonical ZF-DNA interactions ZFP568 forms versatile contacts in response to sequence-specific deformation in DNA Chimp and human ZFP568 have weakened or abolished binding to their Igf2 -P0 sequence Graphical Abstract [DISPLAY OMISSION]

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    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  8. [해외논문]   Dicer-like Enzymes with Sequence Cleavage Preferences  

    Hoehener, Cristina , Hug, Iris , Nowacki, Mariusz
    Cell v.173 no.1 ,pp. 234 - 247.e7 , 2018 , 0092-8674 ,

    초록

    Summary Tandem zinc finger (ZF) proteins are the largest and most rapidly diverging family of DNA-binding transcription regulators in mammals. ZFP568 represses a transcript of placental-specific insulin like growth factor 2 ( Igf2 -P0) in mice. ZFP568 binds a 24-base pair sequence-specific element upstream of Igf2 -P0 via the eleven-ZF array. Both DNA and protein conformations deviate from the conventional one finger-three bases recognition, with individual ZFs contacting 2, 3, or 4 bases and recognizing thymine on the opposite strand. These interactions arise from a shortened minor groove caused by an AT-rich stretch, suggesting adaptability of ZF arrays to sequence variations. Despite conservation in mammals, mutations at Igf2 and ZFP568 reduce their binding affinity in chimpanzee and humans. Our studies provide important insights into the evolutionary and structural dynamics of ZF-DNA interactions that play a key role in mammalian development and evolution. Highlights ZFP568 and its Igf2 -P0 binding activity is conserved in eutheria Mouse ZFP568 11-finger array makes numerous non-canonical ZF-DNA interactions ZFP568 forms versatile contacts in response to sequence-specific deformation in DNA Chimp and human ZFP568 have weakened or abolished binding to their Igf2 -P0 sequence Graphical Abstract [DISPLAY OMISSION]

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  9. [해외논문]   Dicer-like Enzymes with Sequence Cleavage Preferences   SCI SCIE

    Hoehener, Cristina (Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland ) , Hug, Iris (Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland ) , Nowacki, Mariusz (Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland)
    Cell v.173 no.1 ,pp. 234 - 247.e7 , 2018 , 0092-8674 ,

    초록

    Summary Dicer proteins are known to produce small RNAs (sRNAs) from long double-stranded RNA (dsRNA) templates. These sRNAs are bound by Argonaute proteins, which select the guide strand, often with a 5′ end sequence bias. However, Dicer proteins have never been shown to have sequence cleavage preferences. In Paramecium development, two classes of sRNAs that are required for DNA elimination are produced by three Dicer-like enzymes: Dcl2, Dcl3, and Dcl5. Through in vitro cleavage assays, we demonstrate that Dcl2 has a strict size preference for 25 nt and a sequence preference for 5′ U and 5′ AGA, while Dcl3 has a sequence preference for 5′ UNG. Dcl5, however, has cleavage preferences for 5′ UAG and 3′ CUAC/UN, which leads to the production of RNAs precisely matching short excised DNA elements with corresponding end base preferences. Thus, we characterize three Dicer-like enzymes that are involved in Paramecium development and propose a biological role for their sequence-biased cleavage products. Highlights Dicer-like proteins can cleave dsRNA in a sequence-specific manner Dicer-like proteins produce small RNAs with 5′ and 3′ sequence bias Small RNA sequence bias enables precise targeting of transposon-derived IESs Dcl5 recognizes IES-IES junction sequence motifs Graphical Abstract [DISPLAY OMISSION]

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  10. [해외논문]   Chromatin Accessibility Landscape in Human Early Embryos and Its Association with Evolution  

    Gao, Lei , Wu, Keliang , Liu, Zhenbo , Yao, Xuelong , Yuan, Shenli , Tao, Wenrong , Yi, Lizhi , Yu, Guanling , Hou, Zhenzhen , Fan, Dongdong , Tian, Yong , Liu, Jianqiao , Chen, Zi-Jiang , Liu, Jiang
    Cell v.173 no.1 ,pp. 248 - 259.e15 , 2018 , 0092-8674 ,

    초록

    Summary Dicer proteins are known to produce small RNAs (sRNAs) from long double-stranded RNA (dsRNA) templates. These sRNAs are bound by Argonaute proteins, which select the guide strand, often with a 5′ end sequence bias. However, Dicer proteins have never been shown to have sequence cleavage preferences. In Paramecium development, two classes of sRNAs that are required for DNA elimination are produced by three Dicer-like enzymes: Dcl2, Dcl3, and Dcl5. Through in vitro cleavage assays, we demonstrate that Dcl2 has a strict size preference for 25 nt and a sequence preference for 5′ U and 5′ AGA, while Dcl3 has a sequence preference for 5′ UNG. Dcl5, however, has cleavage preferences for 5′ UAG and 3′ CUAC/UN, which leads to the production of RNAs precisely matching short excised DNA elements with corresponding end base preferences. Thus, we characterize three Dicer-like enzymes that are involved in Paramecium development and propose a biological role for their sequence-biased cleavage products. Highlights Dicer-like proteins can cleave dsRNA in a sequence-specific manner Dicer-like proteins produce small RNAs with 5′ and 3′ sequence bias Small RNA sequence bias enables precise targeting of transposon-derived IESs Dcl5 recognizes IES-IES junction sequence motifs Graphical Abstract [DISPLAY OMISSION]

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