| DOI | 10.1038/s41586-020-2336-3
|
| Base-pair conformational switch modulates miR-34a targeting of Sirt1 mRNA |
| Muniz, Juan A.1,2,3; Barberena, Diego1,2,3; Lewis-Swan, Robert J.1,2,3; Young, Dylan J.1,2; Cline, Julia R. K.1,2; Rey, Ana Maria1,2,3; Thompson, James K.1,2
|
| 2020-04-01
|
| 发表期刊 | NATURE
 |
| ISSN | 0028-0836
|
| EISSN | 1476-4687
|
| 出版年 | 2020
|
| 卷号 | 583期号:7814页码:139-+ |
| 文章类型 | Article
|
| 语种 | 英语
|
| 国家 | Sweden; USA; France; Uruguay |
| 英文关键词 | 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.
|
| 领域 | 地球科学
; 气候变化
; 资源环境
|
| 收录类别 | SCI-E
|
| WOS记录号 | WOS:000535878900002
|
| WOS关键词 | EXCITED-STATES
; ARGONAUTE
; GUIDE
; MICRORNAS
; DYNAMICS
; DETERMINANTS
; SIMULATIONS
; PARAMETERS
; CLEAVAGE
|
| WOS类目 | Multidisciplinary Sciences
|
| WOS研究方向 | Science & Technology - Other Topics
|
| 引用统计 |
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| 文献类型 | 期刊论文
|
| 条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/281378
|
| 专题 | 地球科学
资源环境科学
气候变化
|
| 作者单位 | 1.Univ Colorado, NIST, JILA, Boulder, CO 80309 USA;
2.Univ Colorado, Dept Phys, Boulder, CO 80309 USA;
3.Univ Colorado, Ctr Theory Quantum Matter, Boulder, CO 80309 USA
|
推荐引用方式
GB/T 7714 |
Muniz, Juan A.,Barberena, Diego,Lewis-Swan, Robert J.,et al. Base-pair conformational switch modulates miR-34a targeting of Sirt1 mRNA[J].
NATURE,2020,583(7814):139-+.
|
| APA |
Muniz, Juan A..,Barberena, Diego.,Lewis-Swan, Robert J..,Young, Dylan J..,Cline, Julia R. K..,...&Thompson, James K..(2020).Base-pair conformational switch modulates miR-34a targeting of Sirt1 mRNA.NATURE,583(7814),139-+.
|
| MLA |
Muniz, Juan A.,et al."Base-pair conformational switch modulates miR-34a targeting of Sirt1 mRNA".NATURE 583.7814(2020):139-+.
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