Membraneless organelles are cellular compartments made from drops of liquid protein inside a cell. These compartments assemble via the phase separation of disordered regions of proteins in response to changes in the cellular environment and the cell cycle. Here we demonstrate that the solvent environment within the interior of these cellular bodies behaves more like an organic solvent than like water. One of the most-stable biological structures known, the DNA double helix, can be melted once inside the liquid droplet, and simultaneously structures formed from regulatory single-stranded nucleic acids are stabilized. Moreover, proteins are shown to have a wide range of absorption or exclusion from these bodies, and can act as importers for otherwise-excluded nucleic acids, which suggests the existence of a protein-mediated trafficking system. A common strategy in organic chemistry is to utilize different solvents to influence the behaviour of molecules and reactions. These results reveal that cells have also evolved this capability by exploiting the interiors of membraneless organelles.
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A.J.B. thanks the Biotechnology and Biological Sciences Research Council (BBSRC grant BB/J014346/1) for a David Philip's fellowship, and T.D.C. thanks the BBSRC for funding. T.J.N. thanks the BBSRC and New College for funding and O. Tkachenko, G. Hochberg, J. Hopper, S. Chandler and S. Habash for gifts of GFP-tagged proteins, E Fussner-Dupas for antibody-labelling support and B. Davis for discussion and the use of instrumentation. The authors thank L. E. Kay for discussion.
The authors declare no competing financial interests.
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Nott, T., Craggs, T. & Baldwin, A. Membraneless organelles can melt nucleic acid duplexes and act as biomolecular filters. Nature Chem 8, 569–575 (2016). https://doi.org/10.1038/nchem.2519
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