Fine-tuning cellular physiology in response to intracellular and environmental cues requires precise temporal and spatial control of gene expression. High-resolution imaging technologies to detect mRNAs and their translation state have revealed that all living organisms localize mRNAs in subcellular compartments and create translation hotspots, enabling cells to tune gene expression locally. Therefore, mRNA localization is a conserved and integral part of gene expression regulation from prokaryotic to eukaryotic cells. In this Review, we discuss the mechanisms of mRNA transport and local mRNA translation across the kingdoms of life and at organellar, subcellular and multicellular resolution. We also discuss the properties of messenger ribonucleoprotein and higher order RNA granules and how they may influence mRNA transport and local protein synthesis. Finally, we summarize the technological developments that allow us to study mRNA localization and local translation through the simultaneous detection of mRNAs and proteins in single cells, mRNA and nascent protein single-molecule imaging, and bulk RNA and protein detection methods.
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The authors would like to thank the anonymous reviewers for the constructive comments and apologize to collaborators and colleagues whose work could not be cited due to space limitations. This work was supported by NIH grant AG05583 and NSERC grant RGPIN-2019-04767 to M.V., NIH grant NS083085 and NIH Grant GM57071 to R.H.S., and a Rose F. Kennedy IDDRC Pilot Grant to S.D.
The authors declare no competing interests.
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- Signal recognition particle
(SRP). A cytoplasmic RNA–protein complex required for protein targeting to the eukaryotic endoplasmic reticulum or the plasma membrane of bacteria.
- Single-molecule fluorescence in situ hybridization
(smFISH). Fluorescence microscopy-based technique that allows the visualization and quantification of single mRNAs in fixed prokaryotic or eukaryotic cells.
- Patterning factors
Signalling molecules, the distribution pattern of which within an organism contributes to cell differentiation, the determination of anterior–posterior body axis and development.
- SunTag system
Signal amplification system for the visualization of proteins in living or fixed cells. The protein of interest is tagged with a repeated peptide array recognized by a single-chained antibody fused to a fluorescent protein or by immunofluorescence.
The first cleavage of the fertilized C. elegans zygote produces an anterior and a posterior (P1) blastomere. Asymmetric division of P1, until P4 leads to the production of the germline tissue.
- In situ transcriptomics
Imaging-based gene expression and spatial profiling of fixed single cells based on multiple RNA imaging approaches.
Short RNA oligonucleotide, the sequence and structure of which is specifically recognized by an RNA binding protein (for example, the MS2 loop).
(ExFISH). RNA in-situ imaging approach for fixed cells that combines sample clearing and expansion with smFISH, multiplexed smFISH or hybridization chain reaction FISH.
Thin membrane protrusions filled with a dense actin meshwork. They are required for cell forward projection and chemotaxis.
- Cell leading edge
Protrusion of the cell membrane front formed during the migration of epithelial, endothelial, neuronal and immune cells.
- Proximity-dependent biotin identification (BioID) assay
Tool for the identification of protein–protein interactions based on the in vivo labelling with biotin of interactors located in close proximity to the candidate protein.
Proximity labelling of RNA with biotin using the peroxidase enzyme APEX (or APEX2) followed by sequencing.
- Germ granules
RNA-rich membraneless cytoplasmic granules found in the germline of organisms such as X. laevis, D. melanogaster and D. rerio.
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Das, S., Vera, M., Gandin, V. et al. Intracellular mRNA transport and localized translation. Nat Rev Mol Cell Biol 22, 483–504 (2021). https://doi.org/10.1038/s41580-021-00356-8
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