Pisciottani et al. 2023 (PRJNA999250)
General Details
| Title | Reallocation of ribosomes as a disease mechanism of Amyotrophic Lateral Sclerosis |
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| Organism | |
| Number of Samples | 28 |
| Release Date | 2023/07/27 00:00 |
| Sequencing Types | |
| Protocol Details |
Study Links
| GWIPS-viz | Trips-Viz |
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Repository Details
| SRA | SRP451889 |
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| ENA | SRP451889 |
| GEO | GSE239419 |
| BioProject | PRJNA999250 |
Publication
| Title | |
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| Authors | Pisciottani A, Croci L, Lauria F, Marullo C, Savino E, Ambrosi A, Podini P, Marchioretto M, Casoni F, Cremona O, Taverna S, Quattrini A, Cioni JM, Viero G, Codazzi F, Consalez GG |
| Journal | Frontiers in cellular neuroscience |
| Publication Date | 2023 |
| Abstract | Amyotrophic lateral sclerosis (ALS) is a progressive, lethal neurodegenerative disease mostly affecting people around 50-60 years of age. TDP-43, an RNA-binding protein involved in pre-mRNA splicing and controlling mRNA stability and translation, forms neuronal cytoplasmic inclusions in an overwhelming majority of ALS patients, a phenomenon referred to as TDP-43 proteinopathy. These cytoplasmic aggregates disrupt mRNA transport and localization. The axon, like dendrites, is a site of mRNA translation, permitting the local synthesis of selected proteins. This is especially relevant in upper and lower motor neurons, whose axon spans long distances, likely accentuating their susceptibility to ALS-related noxae. In this work we have generated and characterized two cellular models, consisting of virtually pure populations of primary mouse cortical neurons expressing a human TDP-43 fusion protein, wt or carrying an ALS mutation. Both forms facilitate cytoplasmic aggregate formation, unlike the corresponding native proteins, giving rise to bona fide primary culture models of TDP-43 proteinopathy. Neurons expressing TDP-43 fusion proteins exhibit a global impairment in axonal protein synthesis, an increase in oxidative stress, and defects in presynaptic function and electrical activity. These changes correlate with deregulation of axonal levels of polysome-engaged mRNAs playing relevant roles in the same processes. Our data support the emerging notion that deregulation of mRNA metabolism and of axonal mRNA transport may trigger the dying-back neuropathy that initiates motor neuron degeneration in ALS. Copyright © 2023 Pisciottani, Croci, Lauria, Marullo, Savino, Ambrosi, Podini, Marchioretto, Casoni, Cremona, Taverna, Quattrini, Cioni, Viero, Codazzi and Consalez. |
| PMC | PMC10679756 |
| PMID | 38026702 |
| DOI |
| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) | ||
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| SRR25443519 | PRJNA999250 | Mus musculus | 0.0 | Ribo-Seq | 0.0 |  |
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| SRR25443518 | PRJNA999250 | Mus musculus | 0.0 | Ribo-Seq | 0.0 | |
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| SRR25443517 | PRJNA999250 | Mus musculus | 0.0 | Ribo-Seq | 0.0 | |
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| SRR25443516 | PRJNA999250 | Mus musculus | 0.0 | Ribo-Seq | 0.0 | |
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| SRR25443515 | PRJNA999250 | Mus musculus | 0.0 | Ribo-Seq | 0.0 | |
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| SRR25443514 | PRJNA999250 | Mus musculus | 0.0 | Ribo-Seq | 0.0 | |
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| SRR25443513 | PRJNA999250 | Mus musculus | 0.0 | Ribo-Seq | 0.0 | |
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| SRR25443512 | PRJNA999250 | Mus musculus | 0.0 | Ribo-Seq | 0.0 | |
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| SRR25443511 | PRJNA999250 | Mus musculus | 0.0 | free RNA | 0.0 | |
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| SRR25443510 | PRJNA999250 | Mus musculus | 0.0 | free RNA | 0.0 | |
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| SRR25443509 | PRJNA999250 | Mus musculus | 0.0 | polysomal RNA | 0.0 | |
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| SRR25443508 | PRJNA999250 | Mus musculus | 0.0 | polysomal RNA | 0.0 | |
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| SRR25443507 | PRJNA999250 | Mus musculus | 0.0 | free RNA | 0.0 | |
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| SRR25443506 | PRJNA999250 | Mus musculus | 0.0 | free RNA | 0.0 | |
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| SRR25443505 | PRJNA999250 | Mus musculus | 0.0 | polysomal RNA | 0.0 | |
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| SRR25443504 | PRJNA999250 | Mus musculus | 0.0 | polysomal RNA | 0.0 | |
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| SRR25443503 | PRJNA999250 | Mus musculus | 0.0 | free RNA | 0.0 | |
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| SRR25443502 | PRJNA999250 | Mus musculus | 0.0 | free RNA | 0.0 | |
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| SRR25443501 | PRJNA999250 | Mus musculus | 0.0 | free RNA | 0.0 | |
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| SRR25443500 | PRJNA999250 | Mus musculus | 0.0 | polysomal RNA | 0.0 | |
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| SRR25443499 | PRJNA999250 | Mus musculus | 0.0 | polysomal RNA | 0.0 | |
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| SRR25443498 | PRJNA999250 | Mus musculus | 0.0 | polysomal RNA | 0.0 | |
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| SRR25443497 | PRJNA999250 | Mus musculus | 0.0 | free RNA | 0.0 | |
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| SRR25443496 | PRJNA999250 | Mus musculus | 0.0 | free RNA | 0.0 | |
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| SRR25443495 | PRJNA999250 | Mus musculus | 0.0 | free RNA | 0.0 | |
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| SRR25443494 | PRJNA999250 | Mus musculus | 0.0 | polysomal RNA | 0.0 | |
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| SRR25443493 | PRJNA999250 | Mus musculus | 0.0 | polysomal RNA | 0.0 | |
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| SRR25443492 | PRJNA999250 | Mus musculus | 0.0 | polysomal RNA | 0.0 | |
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| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) |
ⓘ For more Information on the columns shown here see: About