ReviewWhy cells move messages: The biological functions of mRNA localization
Section snippets
mRNA localization and the formation of protein gradients
Gradients of morphogens pattern the embryo body plan [6]. They can act as regulators of gene expression that switch on different sets of genes dependent on their concentration along a defined embryonic axis. The first molecularly defined morphogen, Bicoid in Drosophila embryos is encoded by a localized mRNA (for a recent review see Ref. [7]). Bicoid mRNA is localized during oogenesis to the anterior tip of the oocyte where it is anchored. After fertilization, it is translated and a gradient of
mRNA localization and asymmetric distribution of cell fate determinants
Asymmetric cell divisions are widespread in the bacterial and eukaryotic kingdoms [16], [17], [18]. Generally this achieves unequal distribution of different cellular components including nucleic acids and proteins. Numerous mRNAs are asymmetrically distributed upon cell division, especially during early embryogenesis. For many, however, the reason for their asymmetric partitioning is not understood (see, e.g., Ref. [19]). Even in cases where the encoded protein functions as a cell fate
mRNA localization and local assembly of protein complexes
In polarized somatic cells, localized mRNAs can serve as template for spatially restricted synthesis of proteins to maintain cellular asymmetry. In some cases, mRNA localization might also help to facilitate the compartmentalized assembly of multifactor complexes. One of the best-characterized examples for this aspect of mRNA localization is β-actin mRNA in motile cells (Fig. 1C). In several motile cell types, β-actin mRNA is targeted to the leading edge of lamellipodia [32]. These flattened
mRNA localization to the vicinity of organelles
mRNA localization can also facilitate protein sorting to organelles. Generally, protein sorting is based on peptide signals within the protein to be sorted. However, increasing evidence suggests that localization of mRNAs encoding proteins destined to organelles like ER, mitochondria or nuclei supports protein targeting or allows refined targeting that cannot occur on the protein level (see also Dahm et al., this issue).
Vimentin, α-actin, and γ-actin mRNAs display perinuclear localization [33],
Long distance transport of mRNAs and small RNAs in plants
Less is known about RNA localization in the plant kingdom compared to animal cells but a role for RNAs as long-distance information molecules is emerging. The framework for such a mechanism is provided by the plant vascular system. In contrast to animals, higher plants have evolved a unique vascular system that consists of xylem and phloem. Xylem cells allow the delivery of water and minerals, whereas phloem, which consists of living but enucleated sieve elements, transports photo assimilates
Outlook
mRNA localization serves as a sophisticated cellular tool to optimize protein expression on a post-transcriptional level. Besides well-understood functions like generating morphogen gradients or sorting determinants, mRNA localization seems to fulfil a variety of additional roles ranging from facilitated assembly of protein complexes to long-distance signalling and coordination of developmental processes. In addition, new functions have emerged like modulating synaptic plasticity in neurons or
Acknowledgements
R.P.J. and T.G.D. are supported by grants from the Deutsche Forschungsgemeinschaft (DFG JA696/4-4 and SFB646 TPA5).
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Cited by (81)
Organizing the oocyte: RNA localization meets phase separation
2020, Current Topics in Developmental BiologyCitation Excerpt :In some of these examples, the advantages of RNA localization to the cell have not yet been defined. However, well-characterized examples of RNA localization have demonstrated a number of non-mutually exclusive advantages to this process, as detailed below (reviewed in Blower, 2013; Buxbaum, Haimovich, & Singer, 2015; Du, Schmid, & Jansen, 2007; Martin & Ephrussi, 2009; St Johnston, 2005). First, asymmetric enrichment of mRNAs in a particular subcellular domain through RNA localization provides an energetically favorable mechanism to spatially and temporally decouple protein translation from mRNA transcription.
Spatiotemporal Organization of the E. coli Transcriptome: Translation Independence and Engagement in Regulation
2019, Molecular CellCitation Excerpt :Specific localization of mRNAs provides a mechanism for spatiotemporal regulation of protein expression in eukaryotes (Becalska and Gavis, 2009; Donnelly et al., 2010; Du et al., 2007; Martin and Ephrussi, 2009).
Phylogenetic comparison of oskar mRNA localization signals
2014, Biochemical and Biophysical Research CommunicationsAssociation of the yeast RNA-binding protein She2p with the tubular endoplasmic reticulum depends on membrane curvature
2013, Journal of Biological ChemistryProtein targeting to subcellular organelles via mRNA localization
2013, Biochimica et Biophysica Acta - Molecular Cell ResearchCitation Excerpt :While the classical peptide sequence-based targeting pathways to organelles were being dissected, a distinct protein targeting process was discovered by researchers of animal development, neuronal plasticity, and the regulation of mating-type switching in the budding yeast Saccharomyces cerevisiae. In this mode, a cis-acting sequence element in the mRNA specifies its localization in an untranslated state, whereupon translation ensures to produce the protein in the proper location [22,23]. In addition to targeting the protein, this mRNA-based targeting may also function to (i) exclude the protein from intracellular regions where it would be toxic, (ii) circumvent the requirement for other targeting mechanisms, (iii) ensure rapid translational responses to changing abiotic or biotic conditions, (iv) allow the regulation of the protein synthesis by cellular and extracellular stimuli that reflect demand for the product, (v) provide economic benefits from not having to localize the many copies of a protein translated from a single mRNA and (iv) establish “privileged” translation sites that are secluded from other regions under stress.