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.

Activity-dependent expression of RNA binding protein HuD and its association with mRNAs in neurons

“…22,53,54 In addition, the movement of ZBP1-containing granules into dendrites is stimulated by KCl depolarization and is dependent on NMDA receptor activation. 20,55 NMDA receptor activation is also required for the dendritic localization and translation of EGFP-reporter constructs containing cytoplasmic polyadenylation elements (CPEs) found in the 3'UTR of CaMKIIα mRNA. 56 Thus, the activity-dependent dendritic localization as well as expression of HuD parallels these other RBPs known to be involved in synaptic plasticity.…”

Actin-associated hnRNP proteins as transacting factors in the control of mRNA transport and localization

“…3,4 After assembly, RNA granules are sorted to cytoplasmic compartments, a process that appears to be of general importance since it occurs in multiple cell types. 5 The trafficking pathways leading to active RNA sorting are not fully understood at the molecular level, 4 yet they are essential since they lead to the establishment of asymmetric mRNA and protein distribution which in turn allows for specialized cellular functions. Impairment of these mechanisms has considerable physiological consequences.…”

“…6 β-actin mRNA localization to the cell periphery is necessary for cellular motility in fibroblasts and it is also required for neurite outgrowth. 5 In neurons, RNA transport and localized translation are important for axon guidance and synaptic plasticity. 5 In oligodendrocytes, transport and localization of the MBP mRNA to the myelin compartment is likely to be an essential mechanism for myelin biogenesis.…”

“…5 In neurons, RNA transport and localized translation are important for axon guidance and synaptic plasticity. 5 In oligodendrocytes, transport and localization of the MBP mRNA to the myelin compartment is likely to be an essential mechanism for myelin biogenesis. Finally, studies performed in D. melanogaster, C. elegans and X. laevis indicate a role for mRNA trafficking in embryogenesis and organogenesis, 7,8 suggesting an important regulatory function of mRNA localization and transport in controlling gene expression also throughout development.…”

“…β-actin mRNA transport and localization requires a different cis-acting element referred to as zipcode. 5,16 This sequence is located within the 3'UTR of the mature transcript and it is recognized by the zipcode binding protein ZBP1. The zipcode system is utilized for β-actin mRNA transport in fibroblasts and interestingly, also in neurons.…”