RNP granules: Elucidating the steps of neuronal local translation

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Master Thesis

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Abstract

In order to compartmentalizing biochemical processes within the crowded intracellular environment, the cell makes use of organelles. Aside from the well-known membrane-bound organelles, a novel type of organelle is formed by liquid-liquid phase separation into biomolecular condensates. RNP granules are a type of condensates that are enriched in RNA and RNA-binding proteins that play a crucial role in RNA metabolism. They facilitate local translation, which is especially important in highly polarised cells such as neurons where long distances must be bridged. There are several steps in local translation, including RNP granule assembly, transport and mRNA handling and translation. In this review, we will discuss current research on RNP granule assembly and how this can be regulated by post translational modifications. We will discuss mechanisms of their active transport throughout the axon and dendrites by interacting with motor proteins or hitchhiking onto membrane-bound organelles. Then, we will address recent findings on how RNP granules allow for local protein synthesis and if disassembly is essential for mRNA translation. Finally, we summarize the implications of RNP granule components in neurodegenerative diseases and possible mechanisms towards neurodegeneration.

Keywords

RNP granules, Membrane-less organelles, Liquid-liquid phase separation, Local translation, Motor proteins, Active transport, Neurons, Neurodegenerative disease

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