Co-Translational Folding: A Novel Modulator of Local Protein Expression in Mammalian Neurons?

Local protein expression at synapses is a prerequisite for learning in mammalian neurons. It has been shown that a subset of RNAs is localized in dendrites. These transcripts are first assembled into ribonucleoprotein particles in the cell body and are then transported along the cytoskeleton to or near synapses in a translationally repressed state. However, we know very little about the underlying mechanisms of local translation as well as potential protein degradation. Research in the last years showed many features of general translation. One very interesting aspect with raising attention is co-translational folding, a process that guides protein folding during ribosome elongation. In this review, we propose that translation speed is influenced by the codon usage of localized transcripts, which in turn affects protein folding and ultimately degradation efficiency. Together, these processes significantly contribute to synaptic proteome changes and synaptic plasticity. Furthermore, we envision that co-translational misfolding could contribute to neurodegenerative diseases.