Modifiers of solid RNP granules control normal RNP dynamics and mRNA activity in early development

被引:25
作者
Hubstenberger, Arnaud [1 ,3 ]
Cameron, Cristiana [1 ]
Noble, Scott L. [1 ,2 ]
Keenan, Sean [1 ]
Evans, Thomas C. [1 ]
机构
[1] Univ Colorado, Sch Med, Dept Cell & Dev Biol, Aurora, CO 80045 USA
[2] Univ Colorado, Sch Med, Grad Program Mol Biol, Aurora, CO 80045 USA
[3] Univ Paris 06, F-75005 Paris, France
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
CELL-FREE FORMATION; CCR4-NOT COMPLEX; P-GRANULES; FRONTOTEMPORAL DEMENTIA; LATERAL-SCLEROSIS; PHASE-TRANSITIONS; BINDING PROTEINS; ELEGANS HOMOLOG; GENE-EXPRESSION; MRNP GRANULES;
D O I
10.1083/jcb.201504044
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Ribonucleoproteins (RNPs) often coassemble into supramolecular bodies with regulated dynamics. The factors controlling RNP bodies and connections to RNA regulation are unclear. During Caenorhabditis elegans oogenesis, cytoplasmic RNPs can transition among diffuse, liquid, and solid states linked to mRNA regulation. Loss of CGH-1/Ddx6 RNA helicase generates solid granules that are sensitive to mRNA regulators. Here, we identified 66 modifiers of RNP solids induced by cgh-1 mutation. A majority of genes promote or suppress normal RNP body assembly, dynamics, or metabolism. Surprisingly, polyadenylation factors promote RNP coassembly in vivo, suggesting new functions of poly(A) tail regulation in RNP dynamics. Many genes carry polyglutatmine (polyQ) motifs or modulate polyQ aggregation, indicating possible connections with neurodegenerative disorders induced by CAG/polyQ expansion. Several RNP body regulators repress translation of mRNA subsets, suggesting that mRNAs are repressed by multiple mechanisms. Collectively, these findings suggest new pathways of RNP modification that control large-scale coassembly and mRNA activity during development.
引用
收藏
页码:703 / 716
页数:14
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