Dynamic Anchoring of the 3′-End of the Guide Strand Controls the Target Dissociation of Argonaute-Guide Complex

被引：35

作者：

Jung, Seung-Ryoung ^{[1
,2
]}

Kim, Eunji ^{[4
]}

Hwang, Wonseok ^{[1
,2
]}

Shin, Soochul ^{[3
]}

Song, Ji-Joon ^{[4
]}

Hohng, Sungchul ^{[1
,2
,3
]}

机构：

[1] Seoul Natl Univ, Dept Phys & Astron, Seoul 151747, South Korea

[2] Seoul Natl Univ, Natl Ctr Creat Res Initiat, Seoul 151747, South Korea

[3] Seoul Natl Univ, Dept Biophys & Chem Biol, Seoul 151747, South Korea

[4] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2013年 / 135卷 / 45期

基金：

新加坡国家研究基金会;

关键词：

CRYSTAL-STRUCTURE; POSTTRANSCRIPTIONAL REGULATION; RNA INTERFERENCE; RECOGNITION; MECHANISMS; DROSOPHILA; MICRORNAS; BINDING; SIRNAS; CLEAVAGE;

D O I：

10.1021/ja403138d

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Argonaute (Ago) is the catalytic core of small RNA-based gene regulation. Despite plenty of mechanistic studies on Ago, the dynamical aspects and the mechanistic determinants of target mRNA binding and dissociation of Ago guide strand remain unclear. Here, by using single-molecule fluorescence resonance energy transfer (FRET) assays and Thermus thermophilus Ago (TtAgo), we reveal that the 3'-end of the guide strand dynamically anchors at and releases from the PAZ domain of Ago, and that the 3'-end anchoring of the guide strand greatly accelerates the target dissociation by destabilizing the guide-target duplex. Our results indicate that the target binding/dissociation of Ago-guide is executed through the dynamic interplays among Ago, guide, and target.

引用

页码：16865 / 16871

页数：7

共 44 条

[1] Molecular basis for target RNA recognition and cleavage by human RISC
Ameres, Stefan Ludwig
Martinez, Javier
Schroeder, Renee
[J]. CELL, 2007, 130 (01) : 101 - 112
[2] The impact of microRNAs on protein output
Baek, Daehyun
Villen, Judit
Shin, Chanseok
Camargo, Fernando D.
Gygi, Steven P.
Bartel, David P.
[J]. NATURE, 2008, 455 (7209) : 64 - U38
[3] MicroRNAs: Target Recognition and Regulatory Functions
Bartel, David P.
[J]. CELL, 2009, 136 (02) : 215 - 233
[4] Learning Rates and States from Biophysical Time Series: A Bayesian Approach to Model Selection and Single-Molecule FRET Data
Bronson, Jonathan E.
Fei, Jingyi
Hofman, Jake M.
Gonzalez, Ruben L., Jr.
Wiggins, Chris H.
[J]. BIOPHYSICAL JOURNAL, 2009, 97 (12) : 3196 - 3205
[5] Origins and Mechanisms of miRNAs and siRNAs
Carthew, Richard W.
Sontheimer, Erik J.
[J]. CELL, 2009, 136 (04) : 642 - 655
[6] RNA interference is mediated by 21-and 22-nucleotide RNAs
Elbashir, SM
Lendeckel, W
Tuschl, T
[J]. GENES & DEVELOPMENT, 2001, 15 (02) : 188 - 200
[7] Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate
Elbashir, SM
Martinez, J
Patkaniowska, A
Lendeckel, W
Tuschl, T
[J]. EMBO JOURNAL, 2001, 20 (23) : 6877 - 6888
[8] Elkayam E, 2012, CELL, V150, P100, DOI 10.1016/j.cell.2012.05.017
[9] RNAi: The nuts and bolts of the RISC machine
Filipowicz, W
[J]. CELL, 2005, 122 (01) : 17 - 20
[10] Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?
Filipowicz, Witold
Bhattacharyya, Suvendra N.
Sonenberg, Nahum
[J]. NATURE REVIEWS GENETICS, 2008, 9 (02) : 102 - 114

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