Pumilio2 and Staufen2 selectively balance the synaptic proteome

Area of Science:

• Neuroscience
• Molecular Biology
• Cellular Biology

Background:

• Cellular plasticity enables neurons to adapt to environmental stimuli.
• RNA-binding proteins (RBPs) regulate these adaptive processes, but their specific roles are unclear.
• Pumilio2 (Pum2) and Staufen2 (Stau2) are RBPs involved in synaptic transmission.

Purpose of the Study:

• To investigate the distinct impacts of Pum2 and Stau2 on the neuronal transcriptome and proteome.
• To elucidate the roles of Pum2 and Stau2 in regulating synaptic transmission and proteostasis.

Main Methods:

• Depletion of Pum2 and Stau2 in neurons.
• Analysis of transcriptome and proteome changes.
• Measurement of synaptic transmission, including miniature inhibitory postsynaptic currents.
• Investigation of RBP interactions and their effects on gene and protein expression.

Main Results:

• Pum2 and Stau2 exhibit selective impacts on RNA and protein levels despite interacting.
• Pum2 deficiency reduces translation and protein expression.
• Stau2 depletion primarily affects RNA levels, leading to increased protein abundance.
• Pum2 activates expression of GABAergic synaptic components like Gephyrin.
• Pum2 depletion reduces the amplitude of miniature inhibitory postsynaptic currents.

Conclusions:

• RBPs play crucial, selective roles in maintaining proteostasis.
• Distinct RBPs like Pum2 and Stau2 control specific aspects of synaptic transmission.
• Understanding RBP function is key to comprehending neuronal adaptation and plasticity.