Control of translation by eukaryotic mRNA transcript leaders-Insights from high-throughput assays and computational modeling.
Control of translation by eukaryotic mRNA transcript leaders-Insights from high-throughput assays and computational modeling.
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DOI：
10.1002/wrna.1623
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
McManus CJ
中科院分区：
文献类型：
--
作者：
Akirtava C;McManus CJ
真核基因的表达在mRNA向蛋白质的转化过程中受到严格的调控。翻译的错误调节可能导致异常蛋白质在癌症中积聚，并导致神经退行性疾病。对模型基因的基础研究证实了mRNA5‘转录前导序列(TL)在控制核糖体招募、扫描和启动中的基础作用。在非胁迫条件下，TL顺式调控元件及其相应的反式作用因子控制帽依赖的启动。在胁迫下，帽子依赖的启动受到抑制，特定的mRNA结构和序列促进了胁迫反应转录本的翻译，以重塑蛋白质组。在这篇综述中，我们总结了关于目标语在翻译启动中的作用的现有知识。我们集中在核糖体占有率、mRNA结构、RNA结合蛋白占有率和大规模平行报告分析的高通量分析中的见解。这些数据驱动的方法，加上计算分析和建模，为全面理解TL函数铺平了道路。最后，我们将讨论未来关于mRNA序列和结构在翻译中的作用的研究领域。
Eukaryotic gene expression is tightly regulated during translation of mRNA to protein. Mis-regulation of translation can lead to aberrant proteins which accumulate in cancers and cause neurodegenerative diseases. Foundational studies on model genes established fundamental roles for mRNA 5’ transcript leader (TL) sequences in controlling ribosome recruitment, scanning and initiation. TL cis-regulatory elements and their corresponding trans-acting factors control cap-dependent initiation under unstressed conditions. Under stress, cap-dependent initiation is suppressed, and specific mRNA structures and sequences promote translation of stress-responsive transcripts to remodel the proteome. In this review, we summarize current knowledge of TL functions in translation initiation. We focus on insights from high-throughput analyses of ribosome occupancy, mRNA structure, RNA Binding Protein occupancy, and massively parallel reporter assays. These data-driven approaches, coupled with computational analyses and modeling, have paved the way for a comprehensive understanding of TL functions. Finally, we will discuss areas of future research on the roles of mRNA sequences and structures in translation.
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