The Output of Protein-Coding Genes Shifts to Circular RNAs When the Pre-mRNA Processing Machinery Is Limiting.
The Output of Protein-Coding Genes Shifts to Circular RNAs When the Pre-mRNA Processing Machinery Is Limiting.
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DOI：
10.1016/j.molcel.2017.10.034
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发表时间：
2017-12-07
期刊：
影响因子：
16
通讯作者：
Wilusz JE
中科院分区：
文献类型：
--
作者：
Liang D;Tatomer DC;Luo Z;Wu H;Yang L;Chen LL;Cherry S;Wilusz JE
许多真核基因产生线性mRNA和环状RNA，但在很大程度上不知道如何控制或调节线性与环状RNA的比例。利用果蝇细胞中的RNAi筛选，我们确定了许多核心剪接体和转录终止因子，控制报告基因和内源基因的RNA输出。当剪接体成分被耗尽或抑制时，环状RNA的稳态水平增加，而其相关的线性mRNA的表达伴随着减少。在通过切割/聚腺苷酸化机制的耗尽抑制RNA聚合酶II终止后，环状RNA水平类似地增加。这是因为通读转录本现在延伸到下游基因并进行反向剪接。总的来说，这些结果表明，抑制或减缓典型的前mRNA加工事件的蛋白质编码基因的稳态输出转向环状RNA。这部分是因为新生RNA被引导进入导致环状RNA产生的替代途径。许多蛋白质编码基因产生线性mRNA和环状RNA。Liang等人发现，当核心剪接体或转录终止因子从细胞中耗尽时，环状RNA成为优选的基因输出。这部分是因为新生RNA被引导进入导致环状RNA生物合成的替代途径。
Many eukaryotic genes generate linear mRNAs and circular RNAs, but it is largely unknown how the ratio of linear to circular RNA is controlled or modulated. Using RNAi screening in Drosophila cells, we identify many core spliceosome and transcription termination factors that control the RNA outputs of reporter and endogenous genes. When spliceosome components were depleted or inhibited pharmacologically, the steady-state levels of circular RNAs increased while expression of their associated linear mRNAs concomitantly decreased. Upon inhibiting RNA polymerase II termination via depletion of the cleavage/polyadenylation machinery, circular RNA levels were similarly increased. This is because readthrough transcripts now extend into downstream genes and are subjected to backsplicing. In total, these results demonstrate that inhibition or slowing of canonical pre-mRNA processing events shifts the steady-state output of protein-coding genes towards circular RNAs. This is in part because nascent RNAs become directed into alternative pathways that lead to circular RNA production. Many protein-coding genes produce linear mRNAs and circular RNAs. Liang et al. find that circular RNAs become the preferred gene output when core spliceosome or transcription termination factors are depleted from cells. This is in part because nascent RNAs are directed into alternative pathways that lead to circular RNA biogenesis.
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影响因子：
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截止值抑制 RNA 聚合酶 II 终止，以确保 piRNA 前体的表达。
影响因子：
16
作者：
Chen YA;Stuwe E;Luo Y;Ninova M;Le Thomas A;Rozhavskaya E;Li S;Vempati S;Laver JD;Patel DJ;Smibert CA;Lipshitz HD;Toth KF;Aravin AA
通讯作者：
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影响因子：
7
作者：
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