Walking the line: mechanisms underlying directional mRNA transport and localisation in neurons and beyond
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Cellular and Molecular Life Sciences
REVIEW
Walking the line: mechanisms underlying directional mRNA transport and localisation in neurons and beyond Reem Abouward1,2,3 · Giampietro Schiavo1,2 Received: 4 September 2020 / Revised: 2 November 2020 / Accepted: 25 November 2020 © The Author(s) 2020
Abstract Messenger RNA (mRNA) localisation enables a high degree of spatiotemporal control on protein synthesis, which contributes to establishing the asymmetric protein distribution required to set up and maintain cellular polarity. As such, a tight control of mRNA localisation is essential for many biological processes during development and in adulthood, such as body axes determination in Drosophila melanogaster and synaptic plasticity in neurons. The mechanisms controlling how mRNAs are localised, including diffusion and entrapment, local degradation and directed active transport, are largely conserved across evolution and have been under investigation for decades in different biological models. In this review, we will discuss the standing of the field regarding directional mRNA transport in light of the recent discovery that RNA can hitchhike on cytoplasmic organelles, such as endolysosomes, and the impact of these transport modalities on our understanding of neuronal function during development, adulthood and in neurodegeneration. Keywords Axonal transport · Vesicular traffic · Neurodegeneration
The biogenesis and composition of RNA granules From their synthesis, mRNAs interact with several RNA binding proteins (RBPs) that dictate their fate, from splicing and translation to cellular localisation and degradation [1]. RBPs are recruited to mRNAs by binding to specific sequences known as cis-elements and/or by recognising specific secondary and/or tertiary mRNA structures [1, 2]. Ciselements are scattered across the length of the mRNA, but are more frequently found within its 3′-untranslated region (3′-UTR) [3]. Such mRNA and RBP complexes are known as messenger ribonucleoprotein particles (mRNPs). Several mRNPs can come together via protein–protein and RNARNA interactions, forming liquid–liquid phase-separated * Giampietro Schiavo [email protected] 1
Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK
2
UK Dementia Research Institute, University College London, London WC1E 6BT, UK
3
The Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK
RNA granules, such as stress granules and P-bodies [4]. The composition of the granules and the signals that trigger their formation and their subsequent functions, confer to the different RNA granules their unique identities [2]. Relevant to this review are RNA transport granules, in which mRNAs are transported in a likely translationally silent state, until they reach their targets where they undergo local translation in response to specific signals such as external spatial guidance cues [5, 6]. A general conclusion emerging from decades of research, is that the choice of w
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