Axonal mRNA transport and translation at a glance

Sahoo, Pabitra K.; Smith, Deanna S.; Perrone‐Bizzozero, Nora I.; Twiss, Jeffery L.

doi:10.1242/jcs.196808

Cited by 105 publications

(92 citation statements)

References 137 publications

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“…We refer to a number of recent excellent publications for a comprehensive review regarding the role of the 3′ and 5′ UTRs in mediating RNA localization ad gene expression in various cell types, including neurons (Holt and Schuman, 2013; Mayr, 2017; Costa and Willis, 2018; Sahoo et al, 2018). …”

Section: Introductionmentioning

confidence: 99%

Post-transcriptional Processing of mRNA in Neurons: The Vestiges of the RNA World Drive Transcriptome Diversity

Andreassi

Crerar

Riccio

2018

Front. Mol. Neurosci.

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Neurons are morphologically complex cells that rely on the compartmentalization of protein expression to develop and maintain their extraordinary cytoarchitecture. This formidable task is achieved, at least in part, by targeting mRNA to subcellular compartments where they are rapidly translated. mRNA transcripts are the conveyor of genetic information from DNA to the translational machinery, however, they are also endowed with additional functions linked to both the coding sequence (open reading frame, or ORF) and the flanking 5′ and 3′ untranslated regions (UTRs), that may harbor coding-independent functions. In this review, we will highlight recent evidences supporting new coding-dependent and -independent functions of mRNA and discuss how nuclear and cytoplasmic post-transcriptional modifications of mRNA contribute to localization and translation in mammalian cells with specific emphasis on neurons. We also describe recently developed techniques that can be employed to study RNA dynamics at subcellular level in eukaryotic cells in developing and regenerating neurons.

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Section: Introductionmentioning

confidence: 99%

Post-transcriptional Processing of mRNA in Neurons: The Vestiges of the RNA World Drive Transcriptome Diversity

Andreassi

Crerar

Riccio

2018

Front. Mol. Neurosci.

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“…Conversely, miR‐26a is present in dendrites to target MAP2 mRNA, whose protein product is selectively localized in dendrites . Indeed, many miRNAs have also been shown to modulate mRNA translation in dendritic and axonal projections in response to external stimuli . As highlighted here, both noncoding RNAs and RBPs may interact with mRNA transcripts in trans to seed mRNP formation, priming recruitment of effectors to carry out complex regulatory functions including – but not limited to – subcellular targeting.…”

Section: Mechanisms Of Rna Localizationmentioning

confidence: 95%

“…The assembly of RNP complexes, formed by a localized RNA and its associated trans ‐regulators, is thought to be a dynamic process involving distinct regulatory steps carried out in the nucleus and cytoplasm. Indeed, once exported into the cytoplasm, RNPs may be remodeled through the release and acquisition of new components, and may further assemble into higher order transport granules through specific protein‐protein and protein–RNA interactions . For instance, oskar mRNA in the early Drosophila embryo oligomerizes via its 3′UTR, mediated by polypyrimidine tract‐binding protein .…”

Section: Mechanisms Of Rna Localizationmentioning

confidence: 99%

Biological functions, regulatory mechanisms, and disease relevance of RNA localization pathways

et al. 2018

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The asymmetric subcellular distribution of RNA molecules from their sites of transcription to specific compartments of the cell is an important aspect of post-transcriptional gene regulation. This involves the interplay of intrinsic cis-regulatory elements within the RNA molecules with trans-acting RNAbinding proteins and associated factors. Together, these interactions dictate the intracellular localization route of RNAs, whose downstream impacts have wide-ranging implications in cellular physiology. In this review, we examine the mechanisms underlying RNA localization and discuss their biological significance. We also review the growing body of evidence pointing to aberrant RNA localization pathways in the development and progression of diseases.Keywords: Cis-regulatory elements; RNA disease; RNA localization; RNA-binding proteinsThe asymmetric organization of cells is a pervasive feature that ensures the homeostasis of prokaryotic and eukaryotic organisms. This relies on the capacity of cells to organize their contents, including lipids, nucleic acids, and proteins, into specific subcellular structures and organelles. While much of this organization has been attributed to subcellular protein transport [1], a growing body of work indicates that the regulated localization of RNA molecules is also a key process observed across evolutionary timescales [2][3][4][5][6]. This form of post-transcriptional regulation where coding and noncoding RNA molecules actively associate with trans-acting partners, such as RNA-binding proteins (RBPs), serves to dictate both the function and intra-or extracellular destiny of the RNA. During RNA localization, cis-regulatory elements found within the RNA molecule, whether coding or noncoding, act as recognition sites for the recruitment of trans-acting RBPs, which dictate the intra-/extra-cellular fate of the RNA and, ultimately, its functional state. Over the years, the wide-ranging implications of RNA localization on cellular physiology have become apparent, affecting many aspects of cell organization and function. Indeed, RNA localization pathways have been linked to numerous important processes, including developmental patterning, cell polarity, spindle assembly, formation of nonmembranous compartments, localized translation, and cell motility [2][3][4][5][6].

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“…As a consequence of the lack of Golgi in distal dendrites and axons, secretory proteins must be either synthesized and processed in the soma and then trafficked along the axon (which can be as long as 1 m) or dendrite or synthesized locally from mRNA that is actively trafficked along dendrites or axons for local synthesis [70,71]. Membrane proteins synthesized in the soma may also diffuse laterally along the ER membrane for local release at ERES in dendrites and axons [63,72].…”

Section: Er-to-golgi In Neuronsmentioning

confidence: 99%

ER-to-Golgi Trafficking and Its Implication in Neurological Diseases

Wang

Stanford

Kundu

2020

Cells

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Membrane and secretory proteins are essential for almost every aspect of cellular function. These proteins are incorporated into ER-derived carriers and transported to the Golgi before being sorted for delivery to their final destination. Although ER-to-Golgi trafficking is highly conserved among eukaryotes, several layers of complexity have been added to meet the increased demands of complex cell types in metazoans. The specialized morphology of neurons and the necessity for precise spatiotemporal control over membrane and secretory protein localization and function make them particularly vulnerable to defects in trafficking. This review summarizes the general mechanisms involved in ER-to-Golgi trafficking and highlights mutations in genes affecting this process, which are associated with neurological diseases in humans. OverviewApproximately one-third of all proteins encoded by the mammalian genome are exported from the endoplasmic reticulum (ER) and transported to the Golgi apparatus, where they are sorted for delivery to their final destination in membrane compartments or secretory vesicles [1]. Secretory proteins are co-translationally inserted into the ER and then packaged into transport vesicles at ER exit sites (ERES, also known as the transitional ER), which are specialized regions of smooth ER [1].The stepwise process for segregating and exporting cargo from the ER is similar in yeast, plant, and mammalian cells and relies on several essential proteins (SAR1-GTPase, SEC23, SEC24, SEC13, and SEC31). The first step involves the conversion of SAR1-GDP to SAR1-GTP by the guanine nucleotide exchange factor SEC12, which resides in the ER membrane [2,3]. This results in the localization of SAR1-GTP to the ER membrane, triggering the recruitment of SEC23/24 heterodimers [4]. The membrane localization of the SEC23/24 heterodimers promotes the entrapment of cargo by SEC24 and the recruitment of SEC13/31 heterotetramers. The sequential binding of SEC13/31 heterotetramers to SAR1-GTP-SEC23/24 complexes drives the formation of a cage-like lattice [4][5][6][7]. Although the basic steps involved in generating COPII vesicles are well understood and can be reconstituted in vitro, additional proteins are involved in regulating the process in cells. Differences between yeast and mammalian ER-to-Golgi trafficking include the presence of multiple COPII protein isoforms and an ER-Golgi intermediate compartment (ERGIC) in mammals, which likely evolved to help meet the cell-type-specific demands of multicellular organisms.Unlike other cell types, neurons consist of two compartments: the somatodendritic compartment and the axonal compartment. These compartments are separated by the axonal-exclusion zone located at the base of the axon, where proteins are either permitted into or excluded from the axon. Neurons are

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Axonal mRNA transport and translation at a glance

Cited by 105 publications

References 137 publications

Post-transcriptional Processing of mRNA in Neurons: The Vestiges of the RNA World Drive Transcriptome Diversity

Post-transcriptional Processing of mRNA in Neurons: The Vestiges of the RNA World Drive Transcriptome Diversity

Biological functions, regulatory mechanisms, and disease relevance of RNA localization pathways

ER-to-Golgi Trafficking and Its Implication in Neurological Diseases

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