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Localization elements and zip codes in the intracellular transport and localization of messenger RNAs in Saccharomyces cerevisiae

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Abstract Intracellular trafficking and localization of mRNAs provide a mechanism of regulation of expression of genes with excellent spatial control. mRNA localization followed by localized translation appears to be a mechanism of targeted protein sorting to a specific cell‐compartment, which is linked to the establishment of cell polarity, cell asymmetry, embryonic axis determination, and neuronal plasticity in metazoans. However, the complexity of the mechanism and the components of mRNA localization in higher organisms prompted the use of the unicellular organism Saccharomyces cerevisiae as a simplified model organism to study this vital process. Current knowledge indicates that a variety of mRNAs are asymmetrically and selectively localized to the tip of the bud of the daughter cells, to the vicinity of endoplasmic reticulum, mitochondria, and nucleus in this organism, which are connected to diverse cellular processes. Interestingly, specific cis‐acting RNA localization elements (LEs) or RNA zip codes play a crucial role in the localization and trafficking of these localized mRNAs by providing critical binding sites for the specific RNA‐binding proteins (RBPs). In this review, we present a comprehensive account of mRNA localization in S. cerevisiae, various types of localization elements influencing the mRNA localization, and the RBPs, which bind to these LEs to implement a number of vital physiological processes. Finally, we emphasize the significance of this process by highlighting their connection to several neuropathological disorders and cancers. This article is categorized under: RNA Export and Localization > RNA Localization
Schematic diagram showing the molecular events involved in the ASH1 mRNA maturation and localization to the bud tip in Saccharomyces cerevisiae. Molecular components/protein factors involved in the nuclear biogenesis, maturation and localization of the ASH1 mRNA are indicated by various color‐coded symbols. Events involved in specific processes are indicated in the diagram. See text for a detailed description
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Model depicting the nuclear zip code dependent preferential retention of SKS1 (or other) mRNAs in the nucleus of Saccharomyces cerevisiae. (a) SKS1 mRNA harboring the cis‐acting nuclear zip code (indicated in red) element is bound by an unidentified nuclear zipcode binding protein (NZBP), which is expressed in copious amount under high glucose and nitrogen conditions. Binding of the NZBP to SKS1 mRNA eventually prevents the association of SKS1 mRNA with the export factor leading to its slow export and retention in the nucleus. Nuclear retention further causes preferential decay of this mRNA by the nuclear exosome causing a lower steady‐state level and translation in the cytoplasm of SKS1. (b) Under low glucose and nitrogen, the expression of NZBP is dramatically reduced, which facilitates the association of SKS1 mRNA with the export factors leading its rapid export and thereby escapes the nuclear exosome/DRN‐dependent degradation. Increased export subsequently causes higher steady state level and enhanced translation of the message
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Cartoon showing the model of localized translation near outer mitochondrial membrane. mRNAs harboring specific Puf3p binding site at their 3′‐UTR associate with the Puf3p (located in the outer membrane) via specific sequence. This interaction anchors these messages to the outer membrane (OM) without affecting their translation. This proximity of these messages to OM facilitates further interaction of the mitochondrial targeting sequence (MTS) in the nascent polypeptide with Tom20p, which specifies the ribosome attachment to the mitochondrial surface via the interaction between Om14 and NAC with ribosome
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Cartoon depicting the SECReTE dependent localization of mRNAs to the endoplasmic reticulum (ER). Messenger RNAs encoding to the secretory and membrane proteins harbor ER targeting cis‐element, SECReTE. This element enables them to interact and associate with SECReTE‐binding proteins (SBPs). The association of the mRNAs with SBPs subsequently promotes their targeting to ER by a poorly understood fashion. ER targeting subsequently induces ER‐associated translation of these mRNAs followed by the translocation of the nascent polypeptide chains, their folding, modification and finally secretion via secretory pathway. Binding of these mRNA with the SBP potentially enhance their stability and further stimulates their ER association leading to increased secretion (see text for details)
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ASH1 mRNA localization in Saccharomyces cerevisiae. (a) Cartoon showing the events in the ASH1 mRNA localization from nucleus of the mother cell to the bud tip of the daughter cell. (b) Schematic diagram of the position of the localization elements (LEs) E1, E2A, E2B, and E3 in the ASH1 mRNA. Note that while E1, E2A, and E2B are part of ASH1 ORF, E3 is located in the 3′‐UTR. (c) Molecular components/protein factors (RBPs) which bind the ASH1 mRNA during the cytoplasmic transport event. RBPs are indicated by various color‐coded symbols. See text for a detailed description
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