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. 2021 Sep 7;10:e67605. doi: 10.7554/eLife.67605

Figure 9. Model of TDP-43 assemblies in the presence of mRNA.

Figure 9.

(a) Under physiological conditions, an inter-protein interaction (yellow with hatches) involving RRM2 and RRM1 prevents self-attractions of both the N-terminal domain (NTD) and the low complexity domain (LCD) between adjacent TDP-43. (b) When TDP-43 assemblies are no longer stabilized by the RRM-dependent inter-protein interaction, the presence of a RNA linker separating two consecutive TDP-43 leaves room for multivalent interactions between NTDs and LCDs, rendering possible a head-to-tail assembly of TDP-43. (c) The reduced access of mRNA to RRMs in the head-to-tail assembly may explain the transition towards a mRNA-free TDP-43 aggregation.