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Biomolecules
Special Issues
RNA Trafficking and Local Translation in Neuronal Health and Disease
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RNA Trafficking and Local Translation in Neuronal Health and Disease

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: closed (16 December 2019) | Viewed by 20663

Special Issue Editor

Dr. Nobuyuki Shiina

E-Mail Website
Guest Editor
National Institute for Basic Biology and ExCELLS, National Institutes of Natural Sciences, Okazaki, Aichi, Japan
Interests: local translation; synapse formation

Special Issue Information

Dear Colleagues,

mRNA transport and subsequent translation in restricted areas in cells trigger local increase in the concentration and function of specific proteins. In neurons, specific mRNAs are transported to and locally translated in dendrites and axons. Dendritic translation is locally activated by synaptic stimulation, which enables the synapses in the vicinity of the stimulated area to be tagged, thereby leading to potentiation of the limited synapses. This spatiotemporal regulation of synaptic plasticity is associated with learning and memory. On the other hand, axonal translation is locally activated in the growth cone by guidance cues, which leads to axon extension and steering. Axonal local translation is not limited in the growth cone function, but is also involved in multiple roles such as axonal survival, regeneration, and presynaptic function.

mRNAs are transported in RNA-protein (RNP) complexes, which are much larger in dendrites than in axons.  These large complexes are called RNA granules, which contain ribosomes, translation factors, and RNA-binding proteins (RBPs), as well as cargo mRNAs. RNA granules are being revealed to be assembled via liquid-liquid phase separation of RBPs through weak interactions of intrinsically disordered regions (IDRs) of the RBPs. Solidification of RNA granules, caused by mutations and cytoplasmic increase of specific RBPs, is linked to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Other RBP mutations and deficiency, even if without influence on RNA granule assembly, are also linked to psychiatric disorders.

The main goal of this special issue is to highlight recent progress in elucidating the molecular mechanism of the assembly of mRNA transporting complexes, mRNA transport, and local translation in neurons, and furthermore, their roles in neuronal and brain function and dysfunction. This issue welcomes original research articles and reviews related to the keywords listed below.

Dr. Nobuyuki Shiina
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • mRNA transport and local translation in dendrites
  • mRNA transport and local translation in axons
  • RNA granule assembly and dynamics
  • Mechanism for regulation of translation
  • Localized modification and functions of mRNAs and noncoding RNAs
  • Synaptic tagging
  • Synaptic plasticity
  • Learning and memory
  • Axonal growth and guidance
  • Axonal survival and regeneration
  • Aggregation of RNA granules and neurodegenerative diseases
  • Psychiatric disorders

Published Papers (4 papers)

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Review

17 pages, 1323 KiB  
Review
Local Translation in Growth Cones and Presynapses, Two Axonal Compartments for Local Neuronal Functions
by Yukio Sasaki
Biomolecules 2020, 10(5), 668; https://doi.org/10.3390/biom10050668 - 25 Apr 2020
Cited by 8 | Viewed by 4583
Abstract
During neural development, growth cones, very motile compartments of tips of axons, lead axonal extension to the correct targets. Subsequently, presynapses, another axonal compartment with vigorous trafficking of synaptic vesicles, emerge to form functional synapses with postsynapses. In response to extracellular stimuli, the [...] Read more.
During neural development, growth cones, very motile compartments of tips of axons, lead axonal extension to the correct targets. Subsequently, presynapses, another axonal compartment with vigorous trafficking of synaptic vesicles, emerge to form functional synapses with postsynapses. In response to extracellular stimuli, the immediate supply of proteins by local translation within these two axonal compartments far from cell bodies confers high motility of growth cones and active vesicle trafficking in presynapses. Although local translation in growth cones and presynapses occurs at a very low level compared with cell bodies and even dendrites, recent progress in omics and visualization techniques with subcellular fractionation of these compartments has revealed the actual situation of local translation within these two axonal compartments. Here, the increasing evidence for local protein synthesis in growth cones and presynapses for axonal and synaptic functions has been reviewed. Furthermore, the mechanisms regulating local translation in these two compartments and pathophysiological conditions caused by dysregulated local translation are highlighted. Full article
(This article belongs to the Special Issue RNA Trafficking and Local Translation in Neuronal Health and Disease)
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13 pages, 1782 KiB  
Review
Brain Cytoplasmic RNAs in Neurons: From Biosynthesis to Function
by Younghoon Lee, Hee-Seung Lee, Meehyein Kim and Heegwon Shin
Biomolecules 2020, 10(2), 313; https://doi.org/10.3390/biom10020313 - 17 Feb 2020
Cited by 5 | Viewed by 3989
Abstract
Flexibility in signal transmission is essential for high-level brain function. This flexibility is achieved through strict spatial and temporal control of gene expression in neurons. Given the key regulatory roles of a variety of noncoding RNAs (ncRNAs) in neurons, studying neuron-specific ncRNAs provides [...] Read more.
Flexibility in signal transmission is essential for high-level brain function. This flexibility is achieved through strict spatial and temporal control of gene expression in neurons. Given the key regulatory roles of a variety of noncoding RNAs (ncRNAs) in neurons, studying neuron-specific ncRNAs provides an important basis for understanding molecular principles of brain function. This approach will have wide use in understanding the pathogenesis of brain diseases and in the development of therapeutic agents in the future. Brain cytoplasmic RNAs (BC RNAs) are a leading paradigm for research on neuronal ncRNAs. Since the first confirmation of brain-specific expression of BC RNAs in 1982, their investigation has been an area of active research. In this review, we summarize key studies on the characteristics and functions of BC RNAs in neurons. Full article
(This article belongs to the Special Issue RNA Trafficking and Local Translation in Neuronal Health and Disease)
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29 pages, 1250 KiB  
Review
Cataloguing and Selection of mRNAs Localized to Dendrites in Neurons and Regulated by RNA-Binding Proteins in RNA Granules
by Rie Ohashi and Nobuyuki Shiina
Biomolecules 2020, 10(2), 167; https://doi.org/10.3390/biom10020167 - 22 Jan 2020
Cited by 19 | Viewed by 6594
Abstract
Spatiotemporal translational regulation plays a key role in determining cell fate and function. Specifically, in neurons, local translation in dendrites is essential for synaptic plasticity and long-term memory formation. To achieve local translation, RNA-binding proteins in RNA granules regulate target mRNA stability, localization, [...] Read more.
Spatiotemporal translational regulation plays a key role in determining cell fate and function. Specifically, in neurons, local translation in dendrites is essential for synaptic plasticity and long-term memory formation. To achieve local translation, RNA-binding proteins in RNA granules regulate target mRNA stability, localization, and translation. To date, mRNAs localized to dendrites have been identified by comprehensive analyses. In addition, mRNAs associated with and regulated by RNA-binding proteins have been identified using various methods in many studies. However, the results obtained from these numerous studies have not been compiled together. In this review, we have catalogued mRNAs that are localized to dendrites and are associated with and regulated by the RNA-binding proteins fragile X mental retardation protein (FMRP), RNA granule protein 105 (RNG105, also known as Caprin1), Ras-GAP SH3 domain binding protein (G3BP), cytoplasmic polyadenylation element binding protein 1 (CPEB1), and staufen double-stranded RNA binding proteins 1 and 2 (Stau1 and Stau2) in RNA granules. This review provides comprehensive information on dendritic mRNAs, the neuronal functions of mRNA-encoded proteins, the association of dendritic mRNAs with RNA-binding proteins in RNA granules, and the effects of RNA-binding proteins on mRNA regulation. These findings provide insights into the mechanistic basis of protein-synthesis-dependent synaptic plasticity and memory formation and contribute to future efforts to understand the physiological implications of local regulation of dendritic mRNAs in neurons. Full article
(This article belongs to the Special Issue RNA Trafficking and Local Translation in Neuronal Health and Disease)
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23 pages, 2076 KiB  
Review
Translation from the Ribosome to the Clinic: Implication in Neurological Disorders and New Perspectives from Recent Advances
by Kelvin K. Hui, Yi-Kai Chen, Ryo Endo and Motomasa Tanaka
Biomolecules 2019, 9(11), 680; https://doi.org/10.3390/biom9110680 - 1 Nov 2019
Cited by 6 | Viewed by 4947
Abstract
De novo protein synthesis by the ribosome and its multitude of co-factors must occur in a tightly regulated manner to ensure that the correct proteins are produced accurately at the right time and, in some cases, also in the proper location. With novel [...] Read more.
De novo protein synthesis by the ribosome and its multitude of co-factors must occur in a tightly regulated manner to ensure that the correct proteins are produced accurately at the right time and, in some cases, also in the proper location. With novel techniques such as ribosome profiling and cryogenic electron microscopy, our understanding of this basic biological process is better than ever and continues to grow. Concurrently, increasing attention is focused on how translational regulation in the brain may be disrupted during the progression of various neurological disorders. In fact, translational dysregulation is now recognized as the de facto pathogenic cause for some disorders. Novel mechanisms including ribosome stalling, ribosome-associated quality control, and liquid-liquid phase separation are closely linked to translational regulation, and may thus be involved in the pathogenic process. The relationships between translational dysregulation and neurological disorders, as well as the ways through which we may be able to reverse those detrimental effects, will be examined in this review. Full article
(This article belongs to the Special Issue RNA Trafficking and Local Translation in Neuronal Health and Disease)
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