RNA-seq reveals post-transcriptional regulation of Drosophila insulin-like peptide dilp8 and the neuropeptide-like precursor Nplp2 by the exoribonuclease Pacman/XRN1.
RNA-seq reveals post-transcriptional regulation of Drosophila insulin-like peptide dilp8 and the neuropeptide-like precursor Nplp2 by the exoribonuclease Pacman/XRN1.
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DOI：
10.1093/nar/gkv1336
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发表时间：
2016-01-08
影响因子：
14.9
通讯作者：
Newbury SF
中科院分区：
文献类型：
--
作者：
Jones CI;Pashler AL;Towler BP;Robinson SR;Newbury SF
核糖核酸酶在许多细胞和发育过程中至关重要，其表达缺陷与人类疾病有关。Pacman/XRN 1是一种高度保守的胞质核糖核酸外切酶，以5′-3′方向降解RNA。在果蝇中，pacman的无效突变导致小的成虫盘，延迟蛹化的发生和蛹早期的致死性。在本文中，我们使用RNA-seq在全基因组范围内搜索pacman空翼成虫盘中错误调节的mRNA。与对照相比，在pacman无效突变体中只有4.2%的基因被错误调节±>2倍，这与先前的工作一致，表明Pacman对特定的mRNA具有特异性。对上调最多的mRNA的进一步分析表明，Pacman转录后调节分泌的胰岛素样肽Dilp 8的表达。Dilp 8与人IGF-1相关，并且已经显示出在果蝇中协调组织生长与发育时间。Dilp 8的表达增加与pacman无效突变体中观察到的发育延迟一致。我们的分析，加上我们以前的结果，表明，这种外切核糖核酸酶在成虫盘的正常作用是抑制转录的表达，这是至关重要的细胞凋亡和生长控制在正常发育过程中。
Ribonucleases are critically important in many cellular and developmental processes and defects in their expression are associated with human disease. Pacman/XRN1 is a highly conserved cytoplasmic exoribonuclease which degrades RNAs in a 5′-3′ direction. In Drosophila, null mutations in pacman result in small imaginal discs, a delay in onset of pupariation and lethality during the early pupal stage. In this paper, we have used RNA-seq in a genome-wide search for mRNAs misregulated in pacman null wing imaginal discs. Only 4.2% of genes are misregulated ±>2-fold in pacman null mutants compared to controls, in line with previous work showing that Pacman has specificity for particular mRNAs. Further analysis of the most upregulated mRNAs showed that Pacman post-transcriptionally regulates the expression of the secreted insulin-like peptide Dilp8. Dilp8 is related to human IGF-1, and has been shown to coordinate tissue growth with developmental timing in Drosophila. The increased expression of Dilp8 is consistent with the developmental delay seen in pacman null mutants. Our analysis, together with our previous results, show that the normal role of this exoribonuclease in imaginal discs is to suppress the expression of transcripts that are crucial in apoptosis and growth control during normal development.