Hubstenberger Arnaud, Cameron Cristiana, Noble Scott L, Keenan Sean, Evans Thomas C
Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 Pierre-and-Marie-Curie University, University Paris 06, 75005 Paris, France.
Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
J Cell Biol. 2015 Nov 9;211(3):703-16. doi: 10.1083/jcb.201504044. Epub 2015 Nov 2.
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.
核糖核蛋白(RNP)通常会共同组装成具有动态调控的超分子聚集体。控制RNP聚集体以及与RNA调控之间联系的因素尚不清楚。在秀丽隐杆线虫卵子发生过程中,细胞质RNP可以在与mRNA调控相关的弥散态、液态和固态之间转变。CGH-1/Ddx6 RNA解旋酶的缺失会产生对mRNA调节因子敏感的固态颗粒。在这里,我们鉴定出了66个由cgh-1突变诱导产生的RNP固态修饰因子。大多数基因促进或抑制正常RNP聚集体的组装、动态变化或代谢。令人惊讶的是,聚腺苷酸化因子在体内促进RNP共同组装,这表明聚(A)尾调控在RNP动态变化中具有新功能。许多基因带有聚谷氨酰胺(polyQ)基序或调节polyQ聚集,这表明与由CAG/polyQ扩展诱导的神经退行性疾病可能存在关联。几个RNP聚集体调节因子抑制mRNA亚群的翻译,这表明mRNA通过多种机制被抑制。总的来说,这些发现揭示了RNP修饰的新途径,这些途径在发育过程中控制大规模共同组装和mRNA活性。