Visualizing the secondary and tertiary architectural domains of lncRNA RepA.

Visualizing the secondary and tertiary architectural domains of lncRNA RepA.
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DOI:
10.1038/nchembio.2272
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发表时间:
2017-03
影响因子:
14.8
通讯作者:
Pyle AM
Pyle AM
中科院分区:
生物学1区
文献类型:
--
作者:
Liu F;Somarowthu S;Pyle AM

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长链非编码RNA(lncRNA)是基因表达的重要组成部分,但其结构尚不清楚。RepA是一种1.6 kb的小鼠lncRNA,由Xist的5'区中发现的相同序列组成,包括A-和F-重复序列。它被提议促进X染色体失活的启动和传播,尽管其确切作用知之甚少。为了深入了解RepA/Xist的分子机制,我们使用SHAPE和DMS化学探针在体外均匀折叠的RNA确定了RepA的完整和经遗传学验证的二级结构图。UV交联实验与RNA建模方法相结合,产生RepA功能域的三维模型,表明三级结构存在于lncRNA分子内,并发生在特定的功能模块内。这项工作为理解RepA/Xist的进化和功能特性提供了基础,并为探索其他lncRNA的结构特征提供了框架。
Long non-coding RNAs (lncRNAs) are important for gene expression, but little is known about their structures. RepA is a 1.6 kb mouse lncRNA consisting of the same sequence found in the 5’ region of Xist, including A- and F-repeats. It is proposed to facilitate the initiation and spread of X-chromosome inactivation, although its exact role is poorly understood. To gain insight into the molecular mechanism of RepA/Xist, we determined a complete and phylogenetically validated secondary structural map of RepA using SHAPE and DMS chemical probing of a homogeneously folded RNA in vitro. UV crosslinking experiments were combined with RNA modeling methods to produce a three-dimensional model of RepA functional domains, demonstrating that tertiary architecture exists within lncRNA molecules and occurs within specific functional modules. This work provides a foundation for understanding the evolution and functional properties of RepA/Xist and offers a framework for exploring architectural features of other lncRNAs.
地狱1.1:RNA同源性搜索速度更快100倍。
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