Post-transcriptional mechanisms regulate the stability and, hence, expression of coding and noncoding RNAs. Sequence-specific features within the 3' untranslated region (3' UTR) often direct mRNAs for decay. Here, we characterize a genome-wide RNA decay pathway that reduces the half-lives of mRNAs based on overall 3' UTR structure formed by base pairing. The decay pathway is independent of specific single-stranded sequences, as regulation is maintained in both the original and reverse complement orientation. Regulation can be compromised by reducing the overall structure by fusing the 3' UTR with an unstructured sequence. Mutating base-paired RNA regions can also compromise this structure-mediated regulation, which can be restored by re-introducing base-paired structures of different sequences. The decay pathway requires the RNA-binding protein UPF1 and its associated protein G3BP1. Depletion of either protein increased steady-state levels of mRNAs with highly structured 3' UTRs as well as highly structured circular RNAs. This structure-dependent mechanism therefore enables cells to selectively regulate coding and noncoding RNAs.

中文翻译：

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UPF1和G3BP1通过结构介导的RNA衰减。

转录后机制调节稳定性，并因此调节编码和非编码RNA的表达。3'非翻译区（3'UTR）中的序列特异性功能通常指导mRNA衰变。在这里，我们表征了基于碱基配对形成的整体3'UTR结构的全基因组RNA衰变途径，该途径降低了mRNA的半衰期。衰变途径与特定的单链序列无关，因为在原始和反向补体方向上均维持调节。通过将3'UTR与非结构化序列融合来减少整体结构，可以破坏调节。碱基配对的RNA区域发生突变也会破坏这种结构介导的调控，可以通过重新引入不同序列的碱基配对的结构来恢复。衰变途径需要RNA结合蛋白UPF1及其相关蛋白G3BP1。任一种蛋白质的消耗都会增加具有高度结构化的3'UTR和高度结构化的环状RNA的mRNA的稳态水平。因此，这种依赖于结构的机制使细胞能够选择性地调节编码和非编码RNA。