Yi Yung-Hsiang, Ma Tian-Hsiang, Lee Li-Wei, Chiou Pey-Tsyr, Chen Po-Hsiang, Lee Ching-Ming, Chu Yu-De, Yu Hsiang, Hsiung Kuei-Ching, Tsai Yi-Tzang, Lee Chi-Chang, Chang Yu-Sun, Chan Shih-Peng, Tan Bertrand Chin-Ming, Lo Szecheng J
Molecular Medicine Research Center, Chang Gung University, TaoYuan, Taiwan; Department of Biomedical Sciences, College of Medicine, Chang Gung University, TaoYuan, Taiwan.
Department of Biomedical Sciences, College of Medicine, Chang Gung University, TaoYuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, TaoYuan, Taiwan.
PLoS Genet. 2015 Oct 22;11(10):e1005580. doi: 10.1371/journal.pgen.1005580. eCollection 2015 Oct.
Ribosome biogenesis takes place in the nucleolus, the size of which is often coordinated with cell growth and development. However, how metazoans control nucleolar size remains largely unknown. Caenorhabditis elegans provides a good model to address this question owing to distinct tissue distribution of nucleolar sizes and a mutant, ncl-1, which exhibits larger nucleoli than wild-type worms. Here, through a series of loss-of-function analyses, we report that the nucleolar size is regulated by a circuitry composed of microRNA let-7, translation repressor NCL-1, and a major nucleolar pre-rRNA processing protein FIB-1/fibrillarin. In cooperation with RNA binding proteins PUF and NOS, NCL-1 suppressed the translation of FIB-1/fibrillarin, while let-7 targeted the 3'UTR of ncl-1 and inhibited its expression. Consequently, the abundance of FIB-1 is tightly controlled and correlated with the nucleolar size. Together, our findings highlight a novel genetic cascade by which post-transcriptional regulators interplay in developmental control of nucleolar size and function.
核糖体生物合成在核仁中进行,核仁的大小通常与细胞生长和发育相协调。然而,后生动物如何控制核仁大小在很大程度上仍不清楚。秀丽隐杆线虫由于核仁大小的独特组织分布以及一个突变体ncl-1(其核仁比野生型线虫更大),为解决这个问题提供了一个很好的模型。在这里,通过一系列功能丧失分析,我们报告核仁大小受一个由微小RNA let-7、翻译抑制因子NCL-1和一种主要的核仁前体rRNA加工蛋白FIB-1/原纤维蛋白组成的调控回路调节。与RNA结合蛋白PUF和NOS合作,NCL-1抑制FIB-1/原纤维蛋白的翻译,而let-7靶向ncl-1的3'非翻译区并抑制其表达。因此,FIB-1的丰度受到严格控制并与核仁大小相关。总之,我们的发现突出了一种新的遗传级联,通过这种级联,转录后调节因子在核仁大小和功能的发育控制中相互作用。