GSE254209
GSE GEOInhibition of RNA splicing triggers CHMP7 nuclear entry impacting TDP-43 function and leading to onset of ALS (eCLIP).
Relations
Summary
Amyotrophic lateral sclerosis (ALS) has been linked to nucleoporin loss in patient neurons. In the ESCRT-III pathway, CHMP7 protein accumulation in the nucleus triggers ALS by damaging nuclear pores and disrupting cellular transport. Genes controlling CHMP7's nuclear presence remain unidentified. Our Craft-ID analysis revealed that RNA binding proteins involved in assembling small nuclear ribonucleoprotein particles control CHMP7 nuclear localization. This regulation ultimately impacts splicing processes and can lead to pore injury. Using IP-MS, we discovered that CHMP7 interacts with the survival of motor neuron (SMN) complex (SmD1-3, Gemins), mediated by U1 snRNP and direct interactions between CHMP7. Reducing expression of the core SMN complex component SmD1 was observed in ALS iPSC- Motor Neurons (MNs), affecting CHMP7 localization. However, restoring its levels can rescue the cytoplasmic localization of CHMP7 in sALS iPSC-MNs. Our discoveries hint at an early ALS pathway involving SMN core complex dysregulation, influencing disease onset.
Overall Design
eCLIP of CHMP7 in motor neurons, in duplicate
Analysis
View Data ProcessingSupplementary Files (1)
SRA Experiments (12) and Runs (12)
Total: 8077 MBRuns (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR27726268 | 25548423 | 2580390723 | 780.0 | SRA |
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR27726267 | 32714021 | 3304116121 | 1000.0 | SRA |
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR27726266 | 17759440 | 1793703440 | 635.0 | SRA |
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR27726265 | 13560363 | 1369596663 | 449.0 | SRA |
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR27726264 | 31242224 | 3155464624 | 1097.0 | SRA |
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR27726263 | 24243423 | 2448585723 | 768.0 | SRA |
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR27726262 | 9035171 | 912552271 | 283.0 | SRA |
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR27726261 | 25477 | 2573177 | SRA |
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR27726260 | 15625459 | 1578171359 | 528.0 | SRA |
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR27726259 | 21783507 | 2200134207 | 723.0 | SRA |
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR27726258 | 28187168 | 2846903968 | 935.0 | SRA |
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR27726257 | 26278840 | 2654162840 | 879.0 | SRA |
Data Files (12)
| Accession | File Name | Stored Type | Output Type | Mapping Assembly | Size | Download | |
|---|---|---|---|---|---|---|---|
| — | SRR27726257_GSM8036067 | RNA-Seq | 879.0 MB | link | |||
| — | SRR27726258_GSM8036066 | RNA-Seq | 935.0 MB | link | |||
| — | SRR27726259_GSM8036065 | RNA-Seq | 723.0 MB | link | |||
| — | SRR27726260_GSM8036064 | RNA-Seq | 528.0 MB | link | |||
| — | SRR27726261_GSM8036063 | RNA-Seq | link | ||||
| — | SRR27726262_GSM8036062 | RNA-Seq | 283.0 MB | link | |||
| — | SRR27726263_GSM8036061 | RNA-Seq | 768.0 MB | link | |||
| — | SRR27726264_GSM8036060 | RNA-Seq | 1.1 GB | link | |||
| — | SRR27726265_GSM8036059 | RNA-Seq | 449.0 MB | link | |||
| — | SRR27726266_GSM8036058 | RNA-Seq | 635.0 MB | link | |||
| — | SRR27726267_GSM8036057 | RNA-Seq | 1000.0 MB | link | |||
| — | SRR27726268_GSM8036056 | RNA-Seq | 780.0 MB | link |