mRNA Targeting, Transport and Local Translation in Eukaryotic Cells: From the Classical View to a Diversity of New Concepts - PubMed (original) (raw)
mRNA Targeting, Transport and Local Translation in Eukaryotic Cells: From the Classical View to a Diversity of New Concepts
Kseniya A Lashkevich et al. Mol Biol. 2021.
Abstract
Spatial organization of protein biosynthesis in the eukaryotic cell has been studied for more than fifty years, thus many facts have already been included in textbooks. According to the classical view, mRNA transcripts encoding secreted and transmembrane proteins are translated by ribosomes associated with endoplasmic reticulum membranes, while soluble cytoplasmic proteins are synthesized on free polysomes. However, in the last few years, new data has emerged, revealing selective translation of mRNA on mitochondria and plastids, in proximity to peroxisomes and endosomes, in various granules and at the cytoskeleton (actin network, vimentin intermediate filaments, microtubules and centrosomes). There are also long-standing debates about the possibility of protein synthesis in the nucleus. Localized translation can be determined by targeting signals in the synthesized protein, nucleotide sequences in the mRNA itself, or both. With RNA-binding proteins, many transcripts can be assembled into specific RNA condensates and form RNP particles, which may be transported by molecular motors to the sites of active translation, form granules and provoke liquid-liquid phase separation in the cytoplasm, both under normal conditions and during cell stress. The translation of some mRNAs occurs in specialized "translation factories," assemblysomes, transperons and other structures necessary for the correct folding of proteins, interaction with functional partners and formation of oligomeric complexes. Intracellular localization of mRNA has a significant impact on the efficiency of its translation and presumably determines its response to cellular stress. Compartmentalization of mRNAs and the translation machinery also plays an important role in viral infections. Many viruses provoke the formation of specific intracellular structures, virus factories, for the production of their proteins. Here we review the current concepts of the molecular mechanisms of transport, selective localization and local translation of cellular and viral mRNAs, their effects on protein targeting and topogenesis, and on the regulation of protein biosynthesis in different compartments of the eukaryotic cell. Special attention is paid to new systems biology approaches, providing new cues to the study of localized translation.
Keywords: SARS-CoV-2 induced COVID-19; assemblysomes; endoplasmic reticulum; localized translation; mRNA transport; mitochondria; nuclear translation; stress granules; translation factories; viral factories.
© Pleiades Publishing, Inc. 2021, ISSN 0026-8933, Molecular Biology, 2021, Vol. 55, No. 4, pp. 507–537. © Pleiades Publishing, Inc., 2021.
Conflict of interest statement
COMPLIANCE WITH ETHICAL STANDARDSThe authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.
Figures
Fig. 1.
Diversity of mechanisms for protein targeting to the ER and localization of mRNA on the ER membrane. (I) The classic SRP-dependent pathway: the SRP particle, pre-associated with the ribosome, recognizes the signal peptide (SP) or transmembrane domain (TMD) emerging from the ribosomal tunnel, and arrests elongation, after which the transport of the mRNA/ribosome/nascent peptide/SRP complex onto the ER membrane (M) occurs, where SRP binds to its membrane receptor, SR. The translocon (Sec-complex) is involved in the binding of the ribosome on the ER and the translocation of the peptide across the membrane into lumen (L), with the help of proteins associated with the translocon (TRAP, TRAM, OST, etc.). (II) Post-translational mechanism of protein import into the ER mediated by chaperones and other proteins. (III) Localization through the interaction of the synthesized product with the ER resident protein. (IV) Retention of mRNA on the ER membrane in complex with the polysome. (V) Translation-independent mRNA localization mediated by 3'-untranslated region (3'-UTR). Some of the known mRNA-binding proteins involved in various mRNA localization pathways are shown. (VI) Association of the translation complex with the ER through membrane receptors of the ribosome and mRNA-binding proteins.
Fig. 2.
Diversity of mechanisms for proteins targeting in mitochondria. (I) Chaperone-mediated post-translational targeting. (II) Co-translational targeting of the complex consisting of mRNA, ribosome and MTS-containing nascent peptide to the TOM/TIM pore, mediated by NAC (Nascent polypeptide-Associated Complex). (III) Direct binding of NAC to proteins of the outer mitochondrial membrane. (IV) Binding of transcripts to the outer mitochondrial membrane through mRNA-binding proteins. (V) ER-SURF pathway: DJP1-mediated insertion of proteins synthesized on the ER membrane into the mitochondrial membrane. Details are in the text.
Fig. 3.
Translation associated with non-membrane cell organelles. Shown schematically: P-bodies (I); stress granule (II); “ranslation factory” (III); transperon (IV); assemblysome (V); ribosomes and nucleoprotein complexes associated with elements of the cytoskeleton (centrosome and microtubules) (VI). Details are in the text.
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