Decapping is the first committed step in 5′-to-3′ RNA decay, and in the cytoplasm of human cells, multiple decapping enzymes regulate the stabilities of distinct subsets of cellular transcripts. However, the complete set of RNAs regulated by any individual decapping enzyme remains incompletely mapped, and no consensus sequence or property is currently known to unambiguously predict decapping enzyme substrates. Dcp2 was the first-identified and best-studied eukaryotic decapping enzyme, but it has been shown to regulate the stability of <400 transcripts in mammalian cells to date. Here, we globally profile changes in the stability of the human transcriptome in Dcp2 knockout cells via TimeLapse-seq. We find that P-body enrichment is the strongest correlate of Dcp2-dependent decay and that modification with m⁶A exhibits an additive effect with P-body enrichment for Dcp2 targeting. These results are consistent with a model in which P-bodies represent sites where translationally repressed transcripts are sorted for decay by soluble cytoplasmic decay complexes through additional molecular marks.

中文翻译：

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人类 Dcp2 细胞底物的全局分析。

去帽是 5' 到 3' RNA 衰变的第一个重要步骤，在人类细胞的细胞质中，多种去帽酶调节不同细胞转录本子集的稳定性。然而，由任何单个脱帽酶调节的完整 RNA 集仍未完全定位，目前还没有已知的共有序列或特性可以明确预测脱帽酶底物。Dcp2 是第一个鉴定和研究最深入的真核脱帽酶，但迄今为止它已被证明可以调节哺乳动物细胞中<400 个转录本的稳定性。在这里，我们通过 TimeLapse-seq 全局分析了 Dcp2 敲除细胞中人类转录组稳定性的变化。我们发现 P 体富集是 Dcp2 依赖性衰变的最强相关性，并且与 m ⁶A 表现出对 Dcp2 靶向的 P 体富集的累加效应。这些结果与模型一致，其中 P 体代表位点，在这些位点中，翻译抑制的转录本通过额外的分子标记被可溶性细胞质衰变复合物分类为衰变。