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. Author manuscript; available in PMC: 2022 Aug 2.
Published in final edited form as: Cell Rep. 2022 Jul 19;40(3):111106. doi: 10.1016/j.celrep.2022.111106

Figure 7. Mechanisms coupling TDP-43 localization with nuclear GU-rich pre-mRNA binding and abundance.

Figure 7.

(A) Under physiological conditions, nuclear TDP-43 is highly bound to GU-rich nuclear RNAs, limiting the pool of free TDP-43 capable of exiting nuclei by free diffusion through NPCs.

(B) Perturbations that deplete nuclear GU-rich RNAs or impair TDP-43 RNA binding (e.g., transcriptional blockade, RNase, RRM mutations, or putative disruption of GU-RNA homeostasis in disease) cause an initial increase in nuclear free TDP-43, accelerating its passive export until reaching steady state at a lower N/C ratio.

Insets depict the cellular GU-RNA N/C gradients that dictate TDP-43 localization.