A GC-rich sequence feature in the 3' UTR directs UPF1-dependent mRNA decay in mammalian cells.
A GC-rich sequence feature in the 3' UTR directs UPF1-dependent mRNA decay in mammalian cells.
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DOI：
10.1101/gr.206060.116
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发表时间：
2017-03
期刊：
影响因子：
7
通讯作者：
Akimitsu N
中科院分区：
文献类型：
--
作者：
Imamachi N;Salam KA;Suzuki Y;Akimitsu N
上移码蛋白 1 (UPF1) 是一种 ATP 依赖性 RNA 解旋酶，通过促进 mRNA 降解，在 RNA 监视和转录后基因调控中发挥重要作用。先前的研究表明，UPF1 通过尚不清楚的序列特征与目标 mRNA 的 3' 非翻译区 (UTR) 相关。在此，我们的目的是识别 UPF1 目标的特征序列特征。我们通过测量 UPF1 耗尽时的 RNA 稳定性以及识别与 UPF1 相关的 mRNA，确定了 246 个 UPF1 靶点。通过分析磷酸化 UPF1 的 RNA 足迹数据和 UPF1 的两个 CLIP-seq 数据，我们发现 UPF1 靶标的 3'UTR 而不是 5'UTR 或开放阅读框在高 GC 含量区域中嵌入了富含 GC 的基序。报告基因实验表明，UPF1 靶标中富含 GC 的基序对于 UPF1 介导的 mRNA 衰减是不可或缺的。这些发现突出了 UPF1 目标 3' UTR 的重要特征。
Up-frameshift protein 1 (UPF1) is an ATP-dependent RNA helicase that has essential roles in RNA surveillance and in post-transcriptional gene regulation by promoting the degradation of mRNAs. Previous studies revealed that UPF1 is associated with the 3′ untranslated region (UTR) of target mRNAs via as-yet-unknown sequence features. Herein, we aimed to identify characteristic sequence features of UPF1 targets. We identified 246 UPF1 targets by measuring RNA stabilization upon UPF1 depletion and by identifying mRNAs that associate with UPF1. By analyzing RNA footprint data of phosphorylated UPF1 and two CLIP-seq data of UPF1, we found that 3′ UTR but not 5′ UTRs or open reading frames of UPF1 targets have GC-rich motifs embedded in high GC-content regions. Reporter gene experiments revealed that GC-rich motifs in UPF1 targets were indispensable for UPF1-mediated mRNA decay. These findings highlight the important features of UPF1 target 3′ UTRs.