Abstract
Hundreds of messenger RNAs (mRNAs) are transported into neurites to provide templates for the assembly of local protein networks. These networks enable a neuron to configure different cellular domains for specialized functions. According to current evidence, mRNAs are mostly transported in rather small packages of one to three copies, rarely containing different transcripts. This opens up fascinating logistic problems: how are hundreds of different mRNA cargoes sorted into distinct packages and how are they coupled to and released from motor proteins to produce the observed mRNA distributions? Are all mRNAs transported by the same transport machinery, or are there different adaptors or motors for different transcripts or classes of mRNAs? A variety of often indirect evidence exists for the involvement of proteins in mRNA localization, but relatively little is known about the essential activities required for the actual transport process. Here, we summarize the different types of available evidence for interactions that connect mammalian mRNAs to motor proteins to highlight at which point further research is needed to uncover critical missing links. We further argue that a combination of discovery approaches reporting direct interactions, in vitro reconstitution, and fast perturbations in cells is an ideal future strategy to unravel essential interactions and specific functions of proteins in mRNA transport processes.
Highlights
Neuronal messenger RNA localization and local translation are crucial for a range of processes, such as neuronal development (Yoon et al, 2016; Wong et al, 2017), migration (Preitner et al, 2014), polarization (Ciolli Mattioli et al, 2019), and synaptic plasticity (Miller et al, 2002; Donlin-Asp et al, 2021). messenger RNAs (mRNAs) are transported through the cytoplasm as messenger ribonucleoprotein complexes, with a variety of RNA-binding proteins (RBPs) bound to them to control mRNA stability, localization, and translation (Doyle and Kiebler, 2011; Buxbaum et al, 2015)
In order to establish cytoplasmic mRNA distribution, microtubule-based motor proteins, such as mostly microtubule plus-end-directed kinesins and the minus-end-directed dynein, recognize features of messenger ribonucleoprotein (mRNP) that are unknown to a large extent
Mammalian Neuronal mRNA Transport Complexes essential components and the architecture of the mRNA transport machinery, which will allow to disentangle the actual effect of mRNA localization from pleiotropic effects of other components of mRNA transport complexes in the future
Summary
Neuronal messenger RNA (mRNA) localization and local translation are crucial for a range of processes, such as neuronal development (Yoon et al, 2016; Wong et al, 2017), migration (Preitner et al, 2014), polarization (Ciolli Mattioli et al, 2019), and synaptic plasticity (Miller et al, 2002; Donlin-Asp et al, 2021). mRNAs are transported through the cytoplasm as messenger ribonucleoprotein (mRNP) complexes, with a variety of RNA-binding proteins (RBPs) bound to them to control mRNA stability, localization, and translation (Doyle and Kiebler, 2011; Buxbaum et al, 2015). MRNAs are transported through the cytoplasm as messenger ribonucleoprotein (mRNP) complexes, with a variety of RNA-binding proteins (RBPs) bound to them to control mRNA stability, localization, and translation (Doyle and Kiebler, 2011; Buxbaum et al, 2015).
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