scholarly journals Control of cell migration through mRNA localization and local translation

2014 ◽  
Vol 6 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Guoning Liao ◽  
Lisa Mingle ◽  
Livingston Van De Water ◽  
Gang Liu
Keyword(s):  
Cell Migration ◽  
Mrna Localization ◽  
Local Translation

scholarly journals CMTr cap-adjacent 2’-O-ribose mRNA methyltransferases are required for reward learning and mRNA localization to synapses

2021 ◽  
Author(s):  
Irmgard U. Haussmann ◽  
Yanying Wu ◽  
Mohanakarthik P. Nallasivan ◽  
Nathan Archer ◽  
Zsuzsanna Bodi ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Cell Adhesion ◽  
Mushroom Body ◽  
Double Mutant ◽  
Mrna Localization ◽  
Signaling Molecules ◽  
Reward Learning ◽  
Local Translation ◽  
Viral Mrnas ◽  
Conditional Expression

AbstractCap-adjacent nucleotides of animal, protist and viral mRNAs can be dynamically O-methylated at the 2’ position of the ribose (cOMe). The functions of cOMe in animals, however, remain unknown. Here we show that the two cap methyltransferases (CMTr1 and CMTr2) of Drosophila can methylate the ribose of the first nucleotide in mRNA. Double-mutant flies lack cOMe but are viable. Consistent with prominent neuronal expression, they have a reward learning defect that can be rescued by conditional expression in mushroom body neurons before training. Among CMTr targets are cell adhesion and signaling molecules relevant for learning and cOMe is required for local translation of mRNAs at synapses. Hence, our study reveals a mechanism to co-transcriptionally prime mRNAs by cOMe for localized protein synthesis at synapses.

scholarly journals Subcellular sequencing of single neurons reveals the dendritic transcriptome of GABAergic interneurons

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Julio D Perez ◽  
Susanne tom Dieck ◽  
Beatriz Alvarez-Castelao ◽  
Georgi Tushev ◽  
Ivy CW Chan ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Large Population ◽  
Cell Types ◽  
Mrna Localization ◽  
Gabaergic Neurons ◽  
Local Translation ◽  
Single Neurons ◽  
Cell Type ◽  
Cell Type Specific

Although mRNAs are localized in the processes of excitatory neurons, it is still unclear whether interneurons also localize a large population of mRNAs. In addition, the variability in the localized mRNA population within and between cell-types is unknown. Here we describe the unbiased transcriptomic characterization of the subcellular compartments of hundreds of single neurons. We separately profiled the dendritic and somatic transcriptomes of individual rat hippocampal neurons and investigated mRNA abundances in the soma and dendrites of single glutamatergic and GABAergic neurons. We found that, like their excitatory counterparts, interneurons contain a rich repertoire of ~4000 mRNAs. We observed more cell type-specific features among somatic transcriptomes than their associated dendritic transcriptomes. Finally, using cell-type specific metabolic labelling of isolated neurites, we demonstrated that the processes of Glutamatergic and, notably, GABAergic neurons were capable of local translation, suggesting mRNA localization and local translation is a general property of neurons.

scholarly journals Subcellular mRNA localization and local translation of Arhgap11a in radial glial cells regulates cortical development

2020 ◽  
Author(s):  
Louis-Jan Pilaz ◽  
Kaumudi Joshi ◽  
Jing Liu ◽  
Yuji Tsunekawa ◽  
Fernando Alsina ◽  
...  
Keyword(s):  
Glial Cells ◽  
Mrna Localization ◽  
Local Translation ◽  
Control Of Gene Expression ◽  
Radial Glial Cells ◽  
Rhoa Activity ◽  
Cis Element ◽  
Control Brain ◽  
Radial Glial ◽  
Cellular Compartments

mRNA localization and local translation enable exquisite spatial and temporal control of gene expression, particularly in highly polarized and elongated cells. These features are especially prominent in radial glial cells (RGCs), which serve as neural and glial precursors of the developing cerebral cortex, and scaffolds for migrating neurons. Yet the mechanisms by which distinct sub-cellular compartments of RGCs accomplish their diverse functions are poorly understood. Here, we demonstrate that subcellular RNA localization and translation of the RhoGAP Arhgap11a controls RGC morphology and mediates cortical cytoarchitecture. Arhgap11a mRNA and protein exhibit conserved localization to RGC basal structures in mice and humans, conferred by a 5′UTR cis-element. Proper RGC morphology relies upon active Arhgap11a mRNA transport and localization to basal structures, where ARHGAP11A is locally synthesized. Thus, RhoA activity is spatially and acutely activated via local translation in RGCs to promote neuron positioning and cortical cytoarchitecture. Altogether, our study demonstrates that mRNA localization and local translation mediate compartmentalization of neural progenitor functions to control brain development.

scholarly journals A localization screen reveals translation factories and widespread co-translational RNA targeting

2020 ◽  
Author(s):  
Racha Chouaib ◽  
Adham Safieddine ◽  
Xavier Pichon ◽  
Arthur Imbert ◽  
Oh Sung Kwon ◽  
...  
Keyword(s):  
Protein Metabolism ◽  
Mrna Localization ◽  
Local Translation ◽  
Mature Protein ◽  
Control Of Gene Expression ◽  
Spatial Control ◽  
Rna Targeting ◽  
Cycle Dependent ◽  
High Degree ◽  
Quantitation Of Mrna

SummaryLocal translation allows a spatial control of gene expression. Here, we performed a dual protein/mRNA localization screen, using smFISH on 523 human cell lines expressing GFP-tagged genes. A total of 32 mRNAs displayed specific cytoplasmic localizations, and we observed local translation at unexpected locations, including cytoplasmic protrusions, cell edges, endosomes, Golgi, the nuclear envelope and centrosomes, the latter being cell cycle dependent. Quantitation of mRNA distribution and automatic pattern classification revealed a high degree of localization heterogeneity between cells. Surprisingly, mRNA localization frequently required ongoing translation, indicating widespread co-translational RNA targeting. Interestingly, while P-body accumulation was frequent (15 mRNAs), four mRNAs accumulated in foci that were distinct structures. These foci lacked the mature protein, but nascent polypeptide imaging showed that they were specialized translation factories. For β-catenin, foci formation was regulated by Wnt, relied on APC-dependent polysome aggregation, and led to nascent protein degradation. Thus, translation factories uniquely regulate nascent protein metabolism and create a fine granular compartmentalization of translation.

scholarly journals Subcellular mRNA localization regulates ribosome biogenesis in migrating cells

2019 ◽  
Author(s):  
Maria Dermit ◽  
Martin Dodel ◽  
Flora C. Y. Lee ◽  
Muhammad S. Azman ◽  
Hagen Schwenzer ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Progression ◽  
Ribosome Biogenesis ◽  
Epithelial To Mesenchymal Transition ◽  
Rna Binding ◽  
Mrna Localization ◽  
Protein Coding ◽  
Mesenchymal Transition ◽  
Cellular Processes ◽  
Human Breast Carcinomas

AbstractTranslation of Ribosomal Protein-coding mRNAs (RP-mRNAs) constitutes a key step in ribosome biogenesis, but the mechanisms which modulate RP-mRNAs translation in coordination with other cellular processes are poorly defined. Here we show that the subcellular localization of RP-mRNAs acts as a key regulator of their translation during cell migration. As cells migrate into their surroundings, RP-mRNAs localize to actin-rich protrusions at the front the cells. This localization is mediated by La-related protein 6 (LARP6), an RNA binding protein that is enriched in protrusions. Protrusions act as hotspots of translation for RP-mRNAs, resulting in enhancement of ribosome biogenesis and overall protein synthesis, which is required for sustained migration. In human breast carcinomas, Epithelial to Mesenchymal Transition (EMT) upregulates LARP6 expression to enhance ribosome biogenesis and support invasive growth. Our findings reveal LARP6 mediated mRNA localization as a key regulator of ribosome biogenesis during cell migration, and demonstrate a role for this process in cancer progression downstream of EMT.

scholarly journals mRNA localization and local translation in neurons

2020 ◽  
Vol 7 (3) ◽  
pp. 299-310
Author(s):  
Mohammad Mofatteh ◽  
◽  
◽  
Keyword(s):  
Mrna Localization ◽  
Local Translation

scholarly journals Axonal mRNA localization and local translation in neurodegenerative disease

2021 ◽  
Vol 16 (10) ◽  
pp. 1950
Author(s):  
Hai-Ying Li ◽  
Zheng-Quan Yu ◽  
Jin-Xin Lu ◽  
Yang Wang ◽  
Yi-Jie Zhang ◽  
...  
Keyword(s):  
Neurodegenerative Disease ◽  
Mrna Localization ◽  
Local Translation
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