Pnrc2 regulates 3'UTR-mediated decay of segmentation clock-associated transcripts during zebrafish segmentation.
Pnrc2 regulates 3'UTR-mediated decay of segmentation clock-associated transcripts during zebrafish segmentation.
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DOI：
10.1016/j.ydbio.2017.06.024
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发表时间：
2017-09-01
影响因子：
2.7
通讯作者：
Amacher SL
中科院分区：
文献类型：
--
作者：
Gallagher TL;Tietz KT;Morrow ZT;McCammon JM;Goldrich ML;Derr NL;Amacher SL
脊椎动物的分节是由分节时钟控制的，这是一种调节基因表达和快速循环的分子振荡器。许多基因的表达在分裂过程中振荡，包括分裂相关（her或Hes）基因的毛状/增强子，它们编码自动抑制自身表达的转录抑制因子，以及编码Notch配体的deltaC （dlc）。我们之前在斑马鱼循环转录调控基因的前向遗传筛选中发现了tortuga （tor）位点，并发现突变体的循环转录物在剪接后积累。在这里，我们发现突变体中的环状mRNA积累是由于pnrc2的丢失，pnrc2编码一种富含脯氨酸的核受体共激活因子，与mRNA衰变有关。利用可诱导的体内报告系统分析转录物的稳定性，我们发现her1 3'UTR赋予异源转录物依赖pncc2的不稳定性。her1 mRNA衰变与dicer无关，可能使用含有pnrc2 - upf1的mRNA衰变复合物。令人惊讶的是，尽管环状转录本在pnrc2缺陷胚胎中积累，但我们发现环状蛋白的表达正常。总的来说，我们发现Pnrc2促进3 ' utr介导的发育调节的片段时钟转录物的衰变，我们发现了一个额外的转录后调控层，确保在没有环状mRNA衰变的情况下振荡蛋白表达。
Vertebrate segmentation is controlled by the segmentation clock, a molecular oscillator that regulates gene expression and cycles rapidly. The expression of many genes oscillates during segmentation, including hairy/Enhancer of split-related (her or Hes) genes, which encode transcriptional repressors that auto-inhibit their own expression, and deltaC (dlc), which encodes a Notch ligand. We previously identified the tortuga (tor) locus in a zebrafish forward genetic screen for genes involved in cyclic transcript regulation and showed that cyclic transcripts accumulate post-splicing in tor mutants. Here we show that cyclic mRNA accumulation in tor mutants is due to loss of pnrc2, which encodes a proline-rich nuclear receptor co-activator implicated in mRNA decay. Using an inducible in vivo reporter system to analyze transcript stability, we find that the her1 3′UTR confers Pnrc2-dependent instability to a heterologous transcript. her1 mRNA decay is Dicer-independent and likely employs a Pnrc2-Upf1-containing mRNA decay complex. Surprisingly, despite accumulation of cyclic transcripts in pnrc2-deficient embryos, we find that cyclic protein is expressed normally. Overall, we show that Pnrc2 promotes 3′UTR-mediated decay of developmentally-regulated segmentation clock transcripts and we uncover an additional post-transcriptional regulatory layer that ensures oscillatory protein expression in the absence of cyclic mRNA decay.
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影响因子：
14.9
作者：
Fallmann J;Sedlyarov V;Tanzer A;Kovarik P;Hofacker IL
通讯作者：
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影响因子：
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影响因子：
4.6
作者：
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通讯作者：
Oezbudak, Ertugrul M.
DOI：
10.1016/j.bbagrm.2013.10.004
发表时间：
2013-12-01
影响因子：
4.7
作者：
Cho, Hana;Han, Sisu;Kim, Yoon Ki
通讯作者：
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