Details

Autor(en) / Beteiligte

• Sanders, David W.
• Kedersha, Nancy
• Lee, Daniel S.W.
• Strom, Amy R.
• Drake, Victoria
• Riback, Joshua A.
• Bracha, Dan
• Eeftens, Jorine M.
• Iwanicki, Allana
• Wang, Alicia
• Wei, Ming-Tzo
• Whitney, Gena
• Lyons, Shawn M.
• Anderson, Paul
• Jacobs, William M.
• Ivanov, Pavel
• Brangwynne, Clifford P.

Titel

Competing Protein-RNA Interaction Networks Control Multiphase Intracellular Organization

Ist Teil von

• Cell, 2020-04, Vol.181 (2), p.306-324.e28

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• Liquid-liquid phase separation (LLPS) mediates formation of membraneless condensates such as those associated with RNA processing, but the rules that dictate their assembly, substructure, and coexistence with other liquid-like compartments remain elusive. Here, we address the biophysical mechanism of this multiphase organization using quantitative reconstitution of cytoplasmic stress granules (SGs) with attached P-bodies in human cells. Protein-interaction networks can be viewed as interconnected complexes (nodes) of RNA-binding domains (RBDs), whose integrated RNA-binding capacity determines whether LLPS occurs upon RNA influx. Surprisingly, both RBD-RNA specificity and disordered segments of key proteins are non-essential, but modulate multiphase condensation. Instead, stoichiometry-dependent competition between protein networks for connecting nodes determines SG and P-body composition and miscibility, while competitive binding of unconnected proteins disengages networks and prevents LLPS. Inspired by patchy colloid theory, we propose a general framework by which competing networks give rise to compositionally specific and tunable condensates, while relative linkage between nodes underlies multiphase organization. [Display omitted] •Stress granule formation requires RNA-binding nodes with high network connectivity•Capping of nodes by ligands lacking connectivity prevents condensation•Protein disorder and RNA-binding specificity play non-essential, modulatory roles•Competition of RNP networks for connecting nodes controls multiphase organization With sufficient RNA-binding interfaces, diverse protein complexes can trigger stress-dependent multiphase condensates, whose composition and spatial organization is determined by overlapping interaction networks.