A Genetic Cascade of let-7-ncl-1-fib-1 Modulates Nucleolar Size and rRNA Pool in Caenorhabditis elegans.
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.
Molecular Medicine Research Center, Chang Gung University, TaoYuan, Taiwan; Department of Biomedical Sciences, College of Medicine, Chang Gung University, TaoYuan, Taiwan.
Yung-Hsiang
YH
Yi
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.
Tian-Hsiang
TH
Ma
Department of Biomedical Sciences, College of Medicine, Chang Gung University, TaoYuan, Taiwan.
Li-Wei
LW
Lee
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.
Pey-Tsyr
PT
Chiou
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.
Po-Hsiang
PH
Chen
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.
Ching-Ming
CM
Lee
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yu-De
YD
Chu
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.
Hsiang
H
Yu
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.
Kuei-Ching
KC
Hsiung
Molecular Medicine Research Center, Chang Gung University, TaoYuan, Taiwan; Department of Biomedical Sciences, College of Medicine, Chang Gung University, TaoYuan, Taiwan.
Yi-Tzang
YT
Tsai
Department of Biomedical Sciences, College of Medicine, Chang Gung University, TaoYuan, Taiwan.
Chi-Chang
CC
Lee
Molecular Medicine Research Center, Chang Gung University, TaoYuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, TaoYuan, Taiwan.
Yu-Sun
YS
Chang
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan; Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei, Taiwan.
Shih-Peng
SP
Chan
Molecular Medicine Research Center, 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.
Bertrand Chin-Ming
BC
Tan
Molecular Medicine Research Center, 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.
Szecheng J
SJ
Lo
D020413:3' Untranslated Regions; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002466:Cell Nucleolus / Q000235:genetics; D048429:Cell Size; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D005260:Female; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D061848:Optical Imaging; D012335:RNA, Ribosomal / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics* / Q000378:metabolism; D014844:Vulva / Q000254:growth & development / Q000378:metabolism
D020413:3' Untranslated Regions; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D035683:MicroRNAs; D012335:RNA, Ribosomal; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; C047458:fibrillarin; C474488:let-7 microRNA, C elegans; C111448:ncl-1 protein, C elegans