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Common Themes in RNA Subcellular Transport, Stress Granule Formation and Abnormal Protein Aggregation

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Abstract:

Control of protein synthesis and quality are critical steps to support eukaryotic cells' maintenance and survival. Two very distinctive mechanisms emerge as key checkpoints of protein synthesis regulation. The first one is the delivery of mRNA molecules, packed into ribonucleoprotein (mRNP) granules, to specific subcellular regions in order to restrict protein synthesis to distinct cytoplasmic domains. In the presence of cellular stress or injury, translation is aborted by sequestering mRNA molecules into a sub-type of RNP particles called stress granules (SGs). The second mechanism deals with the folding state and further processing of synthesized proteins. Misbehavior of a particular protein, affecting its processing, functioning, and/or conformation can cause the formation of protein inclusions called aggresomes. Interestingly, self-aggregation of abnormal proteins is one of the leading causes of neurodegenerative disorders. Recently, intracellular transport directed by microtubule-motors, has emerged as an important step in the assembly and dynamic of SGs and aggresomes. This mechanism allows for a precise temporal and spatial trafficking of RNA and protein complexes. Furthermore, it facilitates the regulation of the RNA silencing domains and targets abnormal protein aggregates for degradation. In this review we will explore the specific and common features of mRNA transport and of SG and aggresome formation, and will provide details on the role of the microtubule network and motors in their movement and dynamics.





Keywords: Abnormal protein aggregates; Double knockdown (KD) experiments; Drosophila S2 cells; RNA Subcellular Transport; RNP; aggresome; bicoid mRNA; cell stress; cytoskeleton; dynein; kinesin; neurodegenerative disorders; prion-like proteins; stress granules

Document Type: Research Article

DOI: https://doi.org/10.2174/187231311795243373

Publication date: 2011-05-01

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  • Current Chemical Biology aims to publish full-length and mini reviews on exciting new developments at the chemistry-biology interface, covering topics relating to Chemical Synthesis, Science at Chemistry-Biology Interface and Chemical Mechanisms of Biological Systems.

    Current Chemical Biology covers the following areas: Chemical Synthesis (Syntheses of biologically important macromolecules including proteins, polypeptides, oligonucleotides, oligosaccharides etc.; Asymmetric synthesis; Combinatorial synthesis; Diversity-oriented synthesis; Template-directed synthesis; Biomimetic synthesis; Solid phase biomolecular synthesis; Synthesis of small biomolecules: amino acids, peptides, lipids, carbohydrates and nucleosides; and Natural product synthesis).

    Science at Chemistry-Biology Interface (Chemical informatics; Macromolecular catalysts and receptors; Enzymatic synthesis; Biosynthetic engineering; Combinatorial biosynthesis; Plant cell based chemistry; Bacterial and viral cell based chemistry; Chemistry of cellular processes in plants/animals; Receptor chemistry; Cell signaling chemistry; Drug design through understanding of disease processes; Synthetic biology; New high throughput screening techniques; Small molecular array fabrication; Chemical genomics; Chemical and biological approaches to carbohydrates proteins and nucleic acids design; Chemical and biological regulation of biosynthetic pathways; and Unnatural biomolecular analogs).
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