RNA controls PolyQ protein phase transitions

By Huaiying Zhang, Shana Elbaum-Garfinkle, Erin M. Langdon, Nicole Taylor, Patricia Occhipinti, Andrew A. Bridges, C. Brangwynne, A. Gladfelter. Molecules and Cells, 2015

654 citations recorded by the source corpus.

Summary Compartmentalization in cells is central to the spatial and temporal control of biochemistry. In addition to membrane-bound organelles, membrane-less compartments form partitions in cells. Increasing evidence suggests that these compartments assemble through liquid-liquid phase separation. However the spatiotemporal control of their assembly, and how they maintain distinct functional and physical identities is poorly understood. We have previously shown an RNA-binding protein with a polyQ-expansion called Whi3 is essential for the spatial patterning of cyclin and formin transcripts in cytosol. Here, we show that specific mRNAs that are known physiological targets of Whi3 drive phase separation. mRNA can alter the viscosity of droplets, their propensity to fuse, and the exchange rates of components with bulk solution. Different mRNAs impart distinct biophysical properties of droplets indicating mRNA can bring individuality to assemblies. Our findings suggest that mRNAs can encode not only genetic information, but also the biophysical properties of phase-separated compartments.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/731bd45b295dd8c9a145c66771f0b8f54812749e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

Citations in the corpus

Tardigrades use intrinsically disordered proteins to survive desiccation (2018, positive): “In the past two decades, myriad cellular roles for IDPs have emerged, including roles in transcription, post-translational modification, development, cellular organization, and abiotic stress tolerance (Chakrabortee et al., 2012; Garay-Arroyo et al., 2000; Hincha and Thalhammer, 2012; Iakoucheva et ”
Intrinsically disordered regions contribute promiscuous interactions to RNP granule assembly (2017, background): “…other proteins similar to the intracellular environment, despite the observation that such IDRs are capable of undergoing LLPS as purified proteins (Elbaum-Garfinkle et al., 2015; Lin et al., 2015; Molliex et al., 2015; Nott et al., 2015; Patel et al., 2015; Smith et al., 2016; Zhang et al., 2015).”
Principles and Properties of Stress granules (2016, background): “This model has gathered support from the observation that many IDRs from RNP granule components undergo LLPS in vitro, including the RNP granule components hnRNP A1,[39,40] Ddx4, [34] LAF- 1,[42] FUS [51], and Whi3 [52].”
Liquid phase condensation in cell physiology and disease (2017, background): “Entanglement may also be relevant because longer poly(A) RNA (3000 nt) can have the opposite effect, increasing LAF-1 droplet viscosity (46); entanglement could also explain the finding that long RNA increases the viscosity of Whi3 droplets Shin et al., Science 357, eaaf4382 (2017) 22 September 2017”
Distinct stages in stress granule assembly and disassembly (2016, methodology): “…in vitro showing that IDRs from RNA binding proteins can form either LLPS (Lin et al., 2015; Molliex et al., 2015; Murakami et al., 2015; Nott et al., 2015; Zhang et al., 2015) or hydrogels, which in this context are a meshwork assembly of protein filaments (Han et al., 2012; Kato et al., 2012).”
Comprehensive Identification of RNA-Binding Domains in Human Cells (2016, background): “Since YGG repeats are identified as a potential RNA-binding motif in our data set, it will be important to elucidate whether their RNAbinding capacity is affected by the aggregation state and, conversely, whether RNA-binding to such disordered linear motifs can affect phase transitions and granule f”
G3BP–Caprin1–USP10 complexes mediate stress granule condensation and associate with 40S subunits (2016, background): “…granules are composed of immis-cible liquid droplets, held apart from the cytosol by fleeting and multiple low-affinity interactions between LC/ID proteins and RNA (Weber and Brangwynne, 2012; Kroschwald et al., 2015; Lin et al., 2015; Molliex et al., 2015; Nott et al., 2015; Zhang et al., 2015).”
Protein Phase Separation: A New Phase in Cell Biology (2018, background): “RNA can also affect the material properties of protein droplets [48,60].”
Stress-triggered phase separation is an adaptive, evolutionarily tuned response (2017, background): “Previous work on RNA-binding proteins has demonstrated phase separation requiring either an LCR or RNA (Kato et al., 2012; Lin et al., 2015; Molliex et al., 2015; Mugler et al., 2016; Patel et al., 2015; Zhang et al., 2015).”