Insights into the mechanisms of eukaryotic translation gained with ribosome profiling.

Insights into the mechanisms of eukaryotic translation gained with ribosome profiling.
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DOI:
10.1093/nar/gkw1190
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发表时间:
2017-01-25
影响因子:
14.9
通讯作者:
Shatsky IN
Shatsky IN
中科院分区:
生物学2区
文献类型:
--
作者:
Andreev DE;O'Connor PB;Loughran G;Dmitriev SE;Baranov PV;Shatsky IN

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核糖体分析 (RiboSeq) 的发展彻底改变了功能基因组学。 RiboSeq 基于翻译核糖体中包含的 mRNA 片段的捕获和测序,从而提供转录组水平上核糖体位置的“快照”。尽管该方法主要用于分析差异基因表达和发现新的翻译 ORF,但 RiboSeq 数据也可以成为有关多肽合成和翻译控制分子机制的丰富信息来源。本综述将重点关注 RiboSeq 的最新发现如何揭示真核生物翻译分子机制的重要细节。这些包括 mRNA 翻译对影响翻译起始和延伸的药物的敏感性、上游 ORF 在应激反应中的作用、延伸和终止的动态以及翻译终止后 mRNA 上内在核糖体行为的细节。由于 RiboSeq 方法仍处于相对较早的阶段,我们还将讨论 RiboSeq 伪影对数据解释的影响。
The development of Ribosome Profiling (RiboSeq) has revolutionized functional genomics. RiboSeq is based on capturing and sequencing of the mRNA fragments enclosed within the translating ribosome and it thereby provides a ‘snapshot’ of ribosome positions at the transcriptome wide level. Although the method is predominantly used for analysis of differential gene expression and discovery of novel translated ORFs, the RiboSeq data can also be a rich source of information about molecular mechanisms of polypeptide synthesis and translational control. This review will focus on how recent findings made with RiboSeq have revealed important details of the molecular mechanisms of translation in eukaryotes. These include mRNA translation sensitivity to drugs affecting translation initiation and elongation, the roles of upstream ORFs in response to stress, the dynamics of elongation and termination as well as details of intrinsic ribosome behavior on the mRNA after translation termination. As the RiboSeq method is still at a relatively early stage we will also discuss the implications of RiboSeq artifacts on data interpretation.