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Publication : Pumilio2 and Staufen2 selectively balance the synaptic proteome.

First Author  Schieweck R Year  2021
Journal  Cell Rep Volume  35
Issue  12 Pages  109279
PubMed ID  34161769 Mgi Jnum  J:306631
Mgi Id  MGI:6717190 Doi  10.1016/j.celrep.2021.109279
Citation  Schieweck R, et al. (2021) Pumilio2 and Staufen2 selectively balance the synaptic proteome. Cell Rep 35(12):109279
abstractText  Neurons have the capacity to adapt to environmental stimuli, a phenomenon termed cellular plasticity. The underlying processes are controlled by a network of RNA-binding proteins (RBPs). Their precise impact, however, is largely unknown. To address this important question, we chose Pumilio2 (Pum2) and Staufen2 (Stau2), which both regulate synaptic transmission. Surprisingly, even though both RBPs dynamically interact with each other in neurons, their respective impact on the transcriptome and proteome is highly selective. Although Pum2 deficiency leads to reduced translation and protein expression, Stau2 depletion preferentially impacts RNA levels and increases protein abundance. Furthermore, we show that Pum2 activates expression of key GABAergic synaptic components, e.g., the GABA(A) receptor scaffold protein Gephyrin. Consequently, Pum2 depletion selectively reduced the amplitude of miniature inhibitory postsynaptic currents. Together, our data argue for an important role of RBPs to maintain proteostasis in order to control distinct aspects of synaptic transmission.
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