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Membraneless organelles can melt nucleic acid duplexes and act as biomolecular filters


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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Figure 1: Membraneless organelles selectively partition oligonucleotides.
Figure 2: Ddx4N1 organelles destabilize oligonucleotide duplexes.
Figure 3: Ddx4N1 organelle partitioning depends on the stability of the nucleic acid structure.
Figure 4: Ddx4N1 organelles differentially partition proteins, which in turn can act as importers for dsDNA.


  1. Luzio, J. P., Pryor, P. R. & Bright, N. A. Lysosomes: fusion and function. Nature Rev. Mol. Cell Biol. 8, 622–632 (2007).

    CAS  Article  Google Scholar 

  2. Boisvert, F. M., van Koningsbruggen, S., Navascues, J. & Lamond, A. I. The multifunctional nucleolus. Nature Rev. Mol. Cell Biol. 8, 574–585 (2007).

    CAS  Article  Google Scholar 

  3. Nizami, Z., Deryusheva, S. & Gall, J. G. The Cajal body and histone locus body. Cold Spring Harb. Perspect. Biol. 2, 653 (2010).

    Article  Google Scholar 

  4. Anderson, P. & Kedersha, N. RNA granules post-transcriptional and epigenetic modulators of gene expression. Nature Rev. Mol. Cell Biol. 10, 430–436 (2009).

    CAS  Article  Google Scholar 

  5. Brangwynne, C. P. et al. Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science 324, 1729–1732 (2009).

    CAS  Article  Google Scholar 

  6. Brangwynne, C. P., Mitchison, T. J. & Hyman, A. A. Active liquid-like behavior of nucleoli determines their size and shape in Xenopus laevis oocytes. Proc. Natl Acad. Sci. USA 108, 4334–4339 (2011).

    CAS  Article  Google Scholar 

  7. Berry, J., Weber, S. C., Vaidya, N., Haataja, M. & Brangwynne, C. P. RNA transcription modulates phase transition-driven nuclear body assembly. Proc. Natl Acad. Sci. USA 112, E5237–E5245 (2015).

    CAS  Article  Google Scholar 

  8. Nott, T. J. et al. Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles. Mol. Cell 57, 936–947 (2015).

    CAS  Article  Google Scholar 

  9. Li, P. L. et al. Phase transitions in the assembly of multivalent signalling proteins. Nature 483, 336–129 (2012).

    CAS  Article  Google Scholar 

  10. Elbaum-Garfinkle, S. et al. The disordered P granule protein LAF-1 drives phase separation into droplets with tunable viscosity and dynamics. Proc. Natl Acad. Sci. USA 112, 7189–7194 (2015).

    CAS  Article  Google Scholar 

  11. Weber, S. C. & Brangwynne, C. P. Inverse size scaling of the nucleolus by a concentration-dependent phase transition. Curr. Biol. 25, 641–646 (2015).

    CAS  Article  Google Scholar 

  12. Patel, A. et al. A liquid-to-solid phase transition of the ALS protein FUS accelerated by disease mutation. Cell 162, 1066–1077 (2015).

    CAS  Article  Google Scholar 

  13. Lin, Y., Protter, D. S., Rosen, M. K. & Parker, R. Formation and maturation of phase-separated liquid droplets by RNA-binding proteins. Mol. Cell 60, 208–219 (2015).

    CAS  Article  Google Scholar 

  14. Molliex, A. et al. Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization. Cell 163, 123–133 (2015).

    CAS  Article  Google Scholar 

  15. Jiang, H. et al. Phase transition of spindle-associated protein regulate spindle apparatus assembly. Cell 163, 108–122 (2015).

    CAS  Article  Google Scholar 

  16. Burke, K. A., Janke, A. M., Rhine, C. L. & Fawzi, N. L. Residue-by-residue view of in vitro FUS granules that bind the C-terminal domain of RNA polymerase II. Mol. Cell 60, 231–241 (2015).

    CAS  Article  Google Scholar 

  17. Swedlow, J. R. & Lamond, A. I. Nuclear dynamics: where genes are and how they got there. Genome Biol. 2, 2 (2001).

    Article  Google Scholar 

  18. Meikar, O., Da Ros, M., Liljenback, H., Toppari, J. & Kotaja, N. Accumulation of piRNAs in the chromatoid bodies purified by a novel isolation protocol. Exp. Cell Res. 316, 1567–1575 (2010).

    CAS  Article  Google Scholar 

  19. Han, T. N. W. et al. Cell-free formation of RNA granules: bound RNAs identify features and components of cellular assemblies. Cell 149, 768–779 (2012).

    CAS  Article  Google Scholar 

  20. Kato, M. et al. Cell-free formation of RNA granules: low complexity sequence domains form dynamic fibers within hydrogels. Cell 149, 753–767 (2012).

    CAS  Article  Google Scholar 

  21. Pasquinelli, A. E. et al. Conservation of the sequence and temporal expression of Let-7 heterochronic regulatory RNA. Nature 408, 86–89 (2000).

    CAS  Article  Google Scholar 

  22. Reinhart, B. J. et al. The 21-nucleotide Let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403, 901–906 (2000).

    CAS  Article  Google Scholar 

  23. Aravin, A. A. et al. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol. Cell 31, 785–799 (2008).

    CAS  Article  Google Scholar 

  24. Watanabe, T. et al. Identification and characterization of two novel classes of small RNAs in the mouse germline: retrotransposon-derived siRNAs in oocytes and germline small RNAs in testes. Genes Dev. 20, 1732–1743 (2006).

    CAS  Article  Google Scholar 

  25. Baldwin, A. J. et al. Metastability of native proteins and the phenomenon of amyloid formation. J. Am. Chem. Soc. 133, 14160–14163 (2011).

    CAS  Article  Google Scholar 

  26. Borst, J. W., Hink, M. A., van Hoek, A. & Visser, A. J. W. G. Effects of refractive index and viscosity on fluorescence and anisotropy decays of enhanced cyan and yellow fluorescent proteins. J. Fluoresc. 15, 153–160 (2005).

    CAS  Article  Google Scholar 

  27. Suhling, K., Davis, D. M., Petrasek, Z., Siegel, J. & Phillips, D. The influence of the refractive index on EGFP fluorescence lifetimes in mixtures of water and glycerol. Proc. Soc. Photo-Opt. Ins. 2, 92–101 (2001).

    Google Scholar 

  28. Craggs, T. D. Green fluorescent protein: structure, folding and chromophore maturation. Chem. Soc. Rev. 38, 2865–2875 (2009).

    CAS  Article  Google Scholar 

  29. Lawrence, M. S., Phillips, K. J. & Liu, D. R. Supercharging proteins can impart unusual resilience. J. Am. Chem. Soc. 129, 10110–10112 (2007).

    CAS  Article  Google Scholar 

  30. McNaughton, B. R., Cronican, J. J., Thompson, D. B. & Liu, D. R. Mammalian cell penetration, siRNA transfection, and DNA transfection by supercharged proteins. Proc. Natl Acad. Sci. USA 106, 6111–6116 (2009).

    CAS  Article  Google Scholar 

  31. Thiam, A. R., Farese, R. V. & Walther, T. C. The biophysics and cell biology of lipid droplets. Nature Rev. Mol. Cell Biol. 14, 775–786 (2013).

    CAS  Article  Google Scholar 

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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.

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T.J.N., A.J.B. and T.D.C. conceived and designed the experiments; T.J.N. and A.J.B. analysed data and wrote the manuscript with input from T.D.C.; T.J.N. performed the experiments.

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Correspondence to Timothy J. Nott or Andrew J. Baldwin.

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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).

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