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Base-pair conformational switch modulates miR-34a targeting of Sirt1 mRNA 期刊论文
NATURE, 2020, 583 (7814) : 139-+
作者:  Muniz, Juan A.;  Barberena, Diego;  Lewis-Swan, Robert J.;  Young, Dylan J.;  Cline, Julia R. K.;  Rey, Ana Maria;  Thompson, James K.
收藏  |  浏览/下载:60/0  |  提交时间:2020/07/03

MicroRNAs (miRNAs) regulate the levels of translation of messenger RNAs (mRNAs). At present, the major parameter that can explain the selection of the target mRNA and the efficiency of translation repression is the base pairing between the '  seed'  region of the miRNA and its counterpart mRNA(1). Here we use R-1 rho relaxation-dispersion nuclear magnetic resonance(2) and molecular simulations(3) to reveal a dynamic switch-based on the rearrangement of a single base pair in the miRNA-mRNA duplex-that elongates a weak five-base-pair seed to a complete seven-base-pair seed. This switch also causes coaxial stacking of the seed and supplementary helix fitting into human Argonaute 2 protein (Ago2), reminiscent of an active state in prokaryotic Ago(4,5). Stabilizing this transient state leads to enhanced repression of the target mRNA in cells, revealing the importance of this miRNA-mRNA structure. Our observations tie together previous findings regarding the stepwise miRNA targeting process from an initial '  screening'  state to an '  active'  state, and unveil the role of the RNA duplex beyond the seed in Ago2.


Repression of a messenger RNA by a cognate microRNA depends not only on complementary base pairing, but also on the rearrangement of a single base pair, producing a conformation that fits better within the human Ago2 protein.


  
Quantifying the Impact of Uncertainty within the Longitudinal Dispersion Coefficient on Concentration Dynamics and Regulatory Compliance in Rivers 期刊论文
WATER RESOURCES RESEARCH, 2019, 55 (5) : 4393-4409
作者:  Camacho Suarez, V. V.;  Schellart, A. N. A.;  Brevis, W.;  Shucksmith, J. D.
收藏  |  浏览/下载:19/0  |  提交时间:2019/11/26
longitudinal dispersion  river water quality models  advection dispersion equation  parameter uncertainty  dispersion coefficient  ADE analytical solution  
Models of Single-Well Push-Pull Test With Mixing Effect in the Wellbore 期刊论文
WATER RESOURCES RESEARCH, 2018, 54 (12) : 10155-10171
作者:  Wang, Quanrong;  Shi, Wenguang;  Zhan, Hongbin;  Gu, Haochen;  Chen, Kewei
收藏  |  浏览/下载:31/0  |  提交时间:2019/04/09
Radial dispersion  Parameter estimation  Solute transport  Modeling  
Intra-annual rainfall variability in the Spanish hydrographic basins 期刊论文
INTERNATIONAL JOURNAL OF CLIMATOLOGY, 2018, 38 (5) : 2215-2229
作者:  Garcia-Barron, L.;  Aguilar-Alba, M.;  Morales, J.;  Sousa, A.
收藏  |  浏览/下载:9/0  |  提交时间:2019/04/09
intra-annual rainfall  basins  temporal irregularity  centralisation parameter  dispersion parameter  Iberian peninsula  NAO  WeMO