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In the right place at the right time: visualizing and understanding mRNA localization

Nature Reviews Molecular Cell Biology volume 16, pages 95–109 (2015)Cite this article

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A Corrigendum to this article was published on 08 July 2015

This article has been updated

Key Points

  • The asymmetrical distribution of mRNAs in cells is used by various organisms to spatially control gene expression.

  • RNA localization has a role in diverse biological processes, such as development, cell motility, neuron connectivity and mating type switching in yeast.

  • Recent technical advents and the development of new methods for mRNA detection in live and fixed cells allow the tracking and quantification of single mRNAs in a variety of cell types.

  • Single-molecule imaging of mRNA in fixed and live cells revealed a complex cooperativity between RNA-binding proteins (RBPs) and motor proteins to regulate active transport of mRNAs.

  • The composition of mRNA–protein (mRNP) complexes is intricate, and future research will reveal how they assemble into RNA granules with unique localization and functions.

  • Neurons and unicellular organisms, such as yeast and bacteria, use both convergent and disparate mechanisms of targeting mRNAs to different regions.

Abstract

The spatial regulation of protein translation is an efficient way to create functional and structural asymmetries in cells. Recent research has furthered our understanding of how individual cells spatially organize protein synthesis, by applying innovative technology to characterize the relationship between mRNAs and their regulatory proteins, single-mRNA trafficking dynamics, physiological effects of abrogating mRNA localization in vivo and for endogenous mRNA labelling. The implementation of new imaging technologies has yielded valuable information on mRNA localization, for example, by observing single molecules in tissues. The emerging movements and localization patterns of mRNAs in morphologically distinct unicellular organisms and in neurons have illuminated shared and specialized mechanisms of mRNA localization, and this information is complemented by transgenic and biochemical techniques that reveal the biological consequences of mRNA mislocalization.

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Figure 1: Visualizing and understanding mRNA localization in different model systems.
Figure 2: Traditional and novel uses of MS2-like systems to investigate mRNA biology.
Figure 3: Cellular determinants of motored mRNA transport.
Figure 4: mRNA localization in unicellular organisms.
Figure 5: Different types of mRNA movements depend on subcellular location and on cell type.

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Change history

  • 08 July 2015

    In the original article, the two reference citations in the following sentence were incorrect: "... conversely, only 600–800 mammalian RBPs have been recognized so far (Refs 88,89; see the RBP database) ...". The correct references have now been added to the online version of this articleas as references 177 and 178.

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Acknowledgements

The authors are grateful to T. Trcek, R. Lehmann and O. Amster-Choder for contributing their images for Figure 1. The authors also thank E. Tutucci, Y. J. Yoon, S. Preibisch and B. Wu for comments on the manuscript. R.H.S. is funded by the US National Institutes of Health (NIH) grants NIH/NIGMS 2R01GM057071, NIH/NIBIB 5R01EB013571 and NIH/NINDS 9R01NS083085. G.H. is funded by the Gruss Lipper postdoctoral fellowship (EGL charitable foundation) (Albert Einstein College of Medicine), Dean of faculty fellowship (Weizmann Institute of Science (WIS)) and Clore postdoctoral fellowship (WIS).

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Author notes

  1. Gal Haimovich & Robert H. Singer

    Present address: Present address: Department of Molecular Genetics, Weizmann Institute of Science, 234 Herzl Street, Rehovot 7610001, Israel.,

  2. Adina R. Buxbaum and Gal Haimovich: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, 10461, New York, USA

    Adina R. Buxbaum, Gal Haimovich & Robert H. Singer

  2. Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, 10461, New York, USA

    Adina R. Buxbaum, Gal Haimovich & Robert H. Singer

  3. Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, 10461, New York, USA

    Gal Haimovich & Robert H. Singer

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Correspondence to Robert H. Singer.

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Supplementary information

Supplementary information S1 (figure)

Fluorescence in situ hybridization (FISH) technique variations. (PDF 113 kb)

Supplementary information S2 (table)

Visualizing single mRNAs in fixed and live cells (PDF 307 kb)

Supplementary information S3 (movie)

Altered β-actin mRNA behaviour in different cell types. (AVI 13171 kb)

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FURTHER INFORMATION

FISH-quant

RBP database

Glossary

Single-molecule FISH

(smFISH). A fluorescence in situ hybridization (FISH) technique that uses multiple unique short probes against a single mRNA, which greatly increases signal-to-noise ratio and enables detection of single mRNA molecules.

SNAP tag

A protein fusion tag derived from the human enzyme O6-methylguanine DNA methyltransferase. The protein can covalently bind to a synthetic chemical ligand that can be labelled with a fluorescent dye.

Aptamers

Short nucleic acid sequences with unique folding properties that can bind to a specific target molecule and be used for fluorescent tagging.

Myosin

A family of actin-based, ATP-dependent motor proteins.

Kinesin

A class of molecular motors that use ATP to move along microtubule filaments and that transport many cellular components. There are 14 subtypes in the kinesin superfamily, most of which transport cargo to the plus ends of microtubules.

Dynein

A motor protein family that uses ATP to transport cargo along microtubules, typically towards their minus ends. Axonemal dynein has roles in cilia and flagella, whereas cytoplasmic dynein transports mRNAs, among other cargos.

Syncytial blastoderms

A specific stage of Drosophila spp. embryogenesis during which the embryo becomes a single multinucleated cell.

Vegetal cortex

The lower pole on the animal vegetal axis of oocytes where the yolk resides.

Bud tip

The point opposite to the bud neck (which connects the bud to the mother cell) in budding yeast.

Mating type

The budding yeast has two mating types, a and α. Mating of a and α haploid cells produces a diploid cell that can later undergo meiosis to form spores. Haploid cells can switch mating types.

Processing bodies

(P-bodies). Cytoplasmic granules that contain mRNA-degrading proteins, full-length mRNAs and mRNA fragments. Their function is unclear but is related to mRNA degradation.

Synaptic plasticity

Changes in the strength of synaptic transmission in response to changes in synaptic activity, possibly during learning and memory formation.

Long-term potentiation

Long-lasting increase in the efficacy of synaptic transmission between two neurons owing to enhanced neuronal signalling or activity.

HaloTag

A protein fusion tag derived from the enzyme DhaA from Rhodococcus rhodochrous. The protein can covalently bind to a synthetic chemical ligand that can be labelled with a fluorescent dye.

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Buxbaum, A., Haimovich, G. & Singer, R. In the right place at the right time: visualizing and understanding mRNA localization. Nat Rev Mol Cell Biol 16, 95–109 (2015). https://doi.org/10.1038/nrm3918

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