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. 2021 Nov 17;22(12):e53632. doi: 10.15252/embr.202153632

Figure 7. RNA binding is a key driver of TDP‐43 phase separation maintaining liquid properties of the dense state.

Figure 7

  1. Binding of TDP‐43 to GU‐rich RNA promotes liquid properties of TDP‐43 condensates, as shown by the fusion of small condensates into larger droplets. This fluidity is impaired by the loss of RNA‐binding affinity or disease‐linked mutations that alter phase separation, such as M337V and A321G, which could explain increased TDP‐43 aggregation.
  2. RNA molecules that bind multiple TDP‐43 molecules (orange lines) provide a scaffold and increase multivalent interactions, including N‐ and C‐terminal domains, creating a meshwork that results in phase separation. In contrast, nonspecific RNA (blue lines) fails to sufficiently concentrate TDP‐43 to generate the multivalent network necessary for condensation. Scale bars, 10 μm.