Polar Positioning of Phase-Separated Liquid Compartments in Cells Regulated by an mRNA Competition Mechanism.
Polar Positioning of Phase-Separated Liquid Compartments in Cells Regulated by an mRNA Competition Mechanism.
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DOI：
10.1016/j.cell.2016.08.006
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发表时间：
2016-09-08
期刊：
影响因子：
64.5
通讯作者：
Hyman, Anthony A.
中科院分区：
文献类型：
--
作者：
Saha, Shambaditya;Weber, Christoph A.;Nousch, Marco;Adame-Arana, Omar;Hoege, Carsten;Hein, Marco Y.;Osborne-Nishimura, Erin;Mahamid, Julia;Jahnel, Marcus;Jawerth, Louise;Pozniakovski, Andrej;Eckmann, Christian R.;Juelicher, Frank;Hyman, Anthony A.
P颗粒是非膜结合的rna -蛋白区室，参与秀丽隐杆线虫的种系发育。它们是液体，通过局部相分离在胚胎的一端凝结，由极性蛋白质（如mrna结合蛋白MEX-5）的梯度驱动。为了探究极性蛋白如何调节相分离，我们将生物化学和理论建模相结合。我们在体外用单一蛋白PGL-3重建P颗粒样液滴。通过结合体外重建和细胞内浓度的测量，我们发现PGL-3和MEX-5之间对mRNA的竞争可以调节PGL-3液滴的形成。我们利用理论证明，在MEX-5梯度中，这种mRNA竞争机制可以驱动P颗粒组装的梯度，其空间和时间特征与体内P颗粒组装相似。我们得出结论，极性蛋白的梯度可以通过RNA竞争调节局部相分离来定位RNP颗粒。
P granules are non-membrane-bound RNA-protein compartments that are involved in germline development in C. elegans. They are liquids that condense at one end of the embryo by localized phase separation, driven by gradients of polarity proteins such as the mRNA-binding protein MEX-5. To probe how polarity proteins regulate phase separation, we combined biochemistry and theoretical modeling. We reconstitute P granule-like droplets in vitro using a single protein PGL-3. By combining in vitro reconstitution with measurements of intracellular concentrations, we show that competition between PGL-3 and MEX-5 for mRNA can regulate the formation of PGL-3 droplets. Using theory we show that in a MEX-5 gradient, this mRNA competition mechanism can drive a gradient of P granule assembly with similar spatial and temporal characteristics to P granule assembly in vivo. We conclude that gradients of polarity proteins can position RNP granules during development, by using RNA competition to regulate local phase separation.
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影响因子：
64.5
作者：
Griffin EE;Odde DJ;Seydoux G
通讯作者：
Seydoux G
影响因子：
8.6
作者：
Lee, Chiu Fan;Brangwynne, Clifford P.;Juelicher, Frank
通讯作者：
Juelicher, Frank
影响因子：
64.8
作者：
Carazo-Salas, RE;Guarguaglini, G;Mattaj, IW
通讯作者：
Mattaj, IW
DOI：
10.1073/pnas.1509317112
发表时间：
2015-09-22
影响因子：
11.1
作者：
Berry, Joel;Weber, Stephanie C.;Brangwynne, Clifford P.
通讯作者：
Brangwynne, Clifford P.
影响因子：
3.6
作者：
Jahnel, Marcus;Behrndt, Martin;Grill, Stephan W.
通讯作者：
Grill, Stephan W.