The regulatory landscape of 5' UTRs in translational control during zebrafish embryogenesis.
The regulatory landscape of 5' UTRs in translational control during zebrafish embryogenesis.
复制标题
斑马鱼胚胎发生过程中翻译控制中 5UTR 的调控景观。
DOI：
10.1101/2023.11.23.568470
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Schier,AlexF
中科院分区：
文献类型：
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作者：
Reimão-Pinto,MadalenaM;Castillo-Hair,SebastianM;Seelig,Georg;Schier,AlexF
mRNA的5′ UTR在发育过程中对翻译调控至关重要，但其在体内的调控特征尚不清楚。在这里，我们报告了在早期斑马鱼胚胎发育过程中的5′ UTR的监管景观使用大规模平行的报告分析18,154个序列耦合到多核糖体分析。我们发现5′ UTR足以赋予翻译起始时间动力学，并鉴定了86个富含5′ UTR的基序，这些基序具有不同的核糖体募集能力。定量深度学习模型DanioOptimus 5-Prime（DaniO 5 P）确定了5′ UTR长度、翻译起始位点背景、上游AUG和序列基序对核糖体募集的综合作用。DaniO 5 P预测了母体和合子5′ UTR异构体的活性，并表明调节5′ UTR长度和基序语法有助于翻译起始动力学。本研究提供了发育过程中基于5′ UTR的翻译调控的第一个定量模型，并为识别潜在的分子效应器奠定了基础。
The 5′ UTRs of mRNAs are critical for translation regulation during development, but theirin vivoregulatory features are poorly characterized. Here, we report the regulatory landscape of 5′ UTRs during early zebrafish embryogenesis using a massively parallel reporter assay of 18,154 sequences coupled to polysome profiling. We found that the 5′ UTR suffices to confer temporal dynamics to translation initiation and identified 86 motifs enriched in 5′ UTRs with distinct ribosome recruitment capabilities. A quantitative deep learning model,DanioOptimus 5-Prime (DaniO5P), identified a combined role for 5′ UTR length, translation initiation site context, upstream AUGs, and sequence motifs on ribosome recruitment. DaniO5P predicts the activities of maternal and zygotic 5′ UTR isoforms and indicates that modulating 5′ UTR length and motif grammar contributes to translation initiation dynamics. This study provides a first quantitative model of 5′ UTR-based translation regulation in development and lays the foundation for identifying the underlying molecular effectors.