Molecular interactions contributing to FUS SYGQ LC-RGG phase separation and co-partitioning with RNA polymerase II heptads
The RNA-binding protein FUS (Fused in Sarcoma) mediates phase separation in biomolecular condensates and functions in transcription by clustering with RNA polymerase II. Specific contact residues and interaction modes formed by FUS and the C-terminal heptad repeats of RNA polymerase II (CTD) have be...
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Published in | Nature structural & molecular biology Vol. 28; no. 11; pp. 923 - 935 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Nature Publishing Group
01.11.2021
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Subjects | |
Online Access | Get full text |
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Summary: | The RNA-binding protein FUS (Fused in Sarcoma) mediates phase separation in biomolecular condensates and functions in transcription by clustering with RNA polymerase II. Specific contact residues and interaction modes formed by FUS and the C-terminal heptad repeats of RNA polymerase II (CTD) have been suggested but not probed directly. Here we show how RGG domains contribute to phase separation with the FUS N-terminal low-complexity domain (SYGQ LC) and RNA polymerase II CTD. Using NMR spectroscopy and molecular simulations, we demonstrate that many residue types, not solely arginine-tyrosine pairs, form condensed-phase contacts via several interaction modes including, but not only sp
-π and cation-π interactions. In phases also containing RNA polymerase II CTD, many residue types form contacts, including both cation-π and hydrogen-bonding interactions formed by the conserved human CTD lysines. Hence, our data suggest a surprisingly broad array of residue types and modes explain co-phase separation of FUS and RNA polymerase II. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author Contributions Statement A.C.M and N.L.F designed, performed, and analyzed data for NMR spectroscopy, phase separation assays, and microscopy. A.M.J. and D.H.S. performed fluorescence microscopy and provided reagents. T.M.P. assisted with reagents and recorded titration experiments. W.S.T, N.J, and J.M. designed and performed simulation experiments and analyzed the resulting data. A.C.M, J.M., and N.L.F. wrote the manuscript with comments from all authors. WST and NJ (second and third authors) contributed equally |
ISSN: | 1545-9993 1545-9985 |
DOI: | 10.1038/s41594-021-00677-4 |