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Partitioning of cancer therapeutics in nuclear condensates 期刊论文
Science, 2020
作者:  Isaac A. Klein;  Ann Boija;  Lena K. Afeyan;  Susana Wilson Hawken;  Mengyang Fan;  Alessandra Dall'Agnese;  Ozgur Oksuz;  Jonathan E. Henninger;  Krishna Shrinivas;  Benjamin R. Sabari;  Ido Sagi;  Victoria E. Clark;  Jesse M. Platt;  Mrityunjoy Kar;  Patrick M. McCall;  Alicia V. Zamudio;  John C. Manteiga;  Eliot L. Coffey;  Charles H. Li;  Nancy M. Hannett;  Yang Eric Guo;  Tim-Michael Decker;  Tong Ihn Lee;  Tinghu Zhang;  Jing-Ke Weng;  Dylan J. Taatjes;  Arup Chakraborty;  Phillip A. Sharp;  Young Tae Chang;  Anthony A. Hyman;  Nathanael S. Gray;  Richard A. Young
收藏  |  浏览/下载:14/0  |  提交时间:2020/06/22
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:22/0  |  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.


  
Simulating the long-term impacts of drainage and restoration on the ecohydrology of peatlands 期刊论文
WATER RESOURCES RESEARCH, 2017, 53 (8)
作者:  Young, Dylan M.;  Baird, Andy J.;  Morris, Paul J.;  Holden, Joseph
收藏  |  浏览/下载:3/0  |  提交时间:2019/04/09
peatland  drainage  restoration  ecosystem model  long term  carbon  
High permeability explains the vulnerability of the carbon store in drained tropical peatlands 期刊论文
GEOPHYSICAL RESEARCH LETTERS, 2017, 44 (3)
作者:  Baird, Andy J.;  Low, Robert;  Young, Dylan;  Swindles, Graeme T.;  Lopez, Omar R.;  Page, Susan
收藏  |  浏览/下载:11/0  |  提交时间:2019/04/09