Mechanisms and cellular roles of local protein synthesis in mammalian cells

Abstract

After the export from the nucleus it turns out that all mRNAs are not treated equally. Not only is mRNA subject to translation, but also through RNA-binding proteins and other trans-acting factors, eukaryotic cells interpret codes for spatial sorting within the mRNA sequence. These codes instruct the cytoskeleton and translation apparatus to make decisions about where to transport and when to translate the intended protein product. Signaling pathways decode extra-cellular cues and can modify transport and translation factors in the appropriate cytoplasmic space to achieve translation locally. Identifying regulatory sites on transport factors as well as novel physiological functions for well-known translation factors has provided significant advances in how spatially controlled translation impacts cell function.

Figure 1. Spatial control of mRNA translation in neurons

Localizing mRNA to be transported to the neuronal processes begins RNP (L-RNP) formation within the nucleus, helping to ensure stringent translational repression. In the cell soma after export the mRNA (blue line) and associated RNA binding proteins (gray circle) form the L-RNP. In one pathway, an L-RNP is actively transported along the axon (axonal mRNA transport) to the growth cone where guidance cues activate local signal transduction pathways (yellow stars). This activates kinases (open circle; inactive kinase, red circle; activated kinase) that modify components of the transport and/or translation machinery, resulting in local translation (represented by 40S and 60S ribosomal subunits) of the mRNA toward the direction of the guidance cues to aid in navigation of the growth cone. In another pathway an L-RNP is actively transported into the dendrites (dendritic mRNA transport). At the post-synaptic region of activated synapses (green pre-synaptic terminal) synaptic activity activates signal transduction pathways, activating kinases that modify components of the transport and/or translation machinery, resulting in local translation of the mRNA in the vicinity of the guidance cues. The lack of activated kinases at non-stimulated synapses (red pre-synaptic terminal) does not cause translational de-repression at these sites.