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Control of cell migration through mRNA localization and local translation

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Cell migration plays an important role in many normal and pathological functions such as development, wound healing, immune defense, and tumor metastasis. Polarized migrating cells exhibit asymmetric distribution of many cytoskeletal proteins, which is believed to be critical for establishing and maintaining cell polarity and directional cell migration. To target these proteins to the site of function, cells use a variety of mechanisms such as protein transport and messenger RNA (mRNA) localization‐mediated local protein synthesis. In contrast to the former which is intensively investigated and relatively well understood, the latter has been understudied and relatively poorly understood. However, recent advances in the study of mRNA localization and local translation have demonstrated that mRNA localization and local translation are specific and effective ways for protein localization and are crucial for embryo development, neuronal function, and many other cellular processes. There are excellent reviews on mRNA localization, transport, and translation during development and other cellular processes. This review will focus on mRNA localization‐mediated local protein biogenesis and its impact on somatic cell migration. WIREs RNA 2015, 6:1–15. doi: 10.1002/wrna.1265 This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications Translation > Translation Regulation RNA Export and Localization > RNA Localization
Arp3 protein and messenger RNA (mRNA) are localized at the cell leading protrusions in wound tissue. Day 4 rat skin wound tissue cryosections were processed for protein using immunofluorescence staining (a) or for mRNA using fluorescence in situ hybridization with tyramide signal amplification (b). To present a whole 10‐µm cryosection, 10 digital images of optical Z‐sections (1 µm each) were deconvolved to remove out‐focus fluorescence and then projected along the z axis. Note in (a) that the stationary keratinocytes over the wound bed (above the dotted line) exhibit a relatively uniform distribution of Arp3 protein. The Arp2/3 is a very stable protein complex, and detection of one member is indicative of the location of this protein complex. Arrows point to the localized protein (red in a) and arrowheads point to localized mRNA (green in b) (Mingle et al., unpublished data).
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Differential intracellular distribution of the Arp2/3 mRNA and Dia1 mRNA in fibroblasts. Representative intracellular distribution of Arp2 mRNA (green) and Dia1 mRNA (red) in the CEFs. Dashed lines indicate cell border and blue for nucleus. Arp2 mRNA (green) is concentrated at the leading lamella while the Dia1 mRNA (red) is perinuclear. Similar differential distribution of the Arp2/3 complex mRNAs and Dia1 mRNA was also observed in human foreskin fibroblasts (not shown). (Reprinted with permission from Ref . Copyright 2011 The Company of Biologists)
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Visualization of Arp2 mRNA movement in live fibroblasts. (a) Illustration of the MS2 system for visualization of RNA in live cells. The phage MS2 coat protein (MCP) is fused with green fluorescence protein (GFP), and a nuclear localization signal (NLS) tag that sequesters the MCP‐GFP in the nucleus if it is not bound to the mRNA. The MS2 stem‐loop repeat is inserted into the 3′UTR of Arp2 mRNA. The MCP‐GFP protein binds to the MS2 RNA repeat with high affinity so the location of the mRNA can be detected by the GFP fluorescence. (b) Still images from a 1‐h time lapse show the dynamic movement of the Arp2 mRNA in a fibroblast cell. Arrows point to the protrusions and arrowheads point to the nucleus in which the unbound MCP‐GFP is sequestered (Mingle and Liu, unpublished data).
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RNA Export and Localization > RNA Localization
RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
Translation > Translation Regulation

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