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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 01, 2023 |
| Title |
RNA-Seq of neural stem cells from Wild Type (WT) and Armc5 knockout mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
ARMC5 is a protein containing an armadillo domain (ARM) and a BTB domain. Its gene knockout caused many phenotypes, including dwarfism, compromise T-cell immunity, and adrenal gland hypertrophy. ARMC5 mutation in humans is associated with bilateral macronodular adrenal gland hypertrophy. We found that AMC5 KO mice suffered from an increased incidence of neural tube defects (NTDs). We revealed that ARMC5 complexed with CUL3 and POLR2A and was part of a novel POLR2A-specific ubiquitin ligase (E3). This E3 was the dominant DNA damage-independent POLR2A-specific E3 in developing neural tubes and neural precursor cells under a physiological condition. ARMC5 gene knockout (KO) caused diminished POLR2A ubiquitination and compromised POLR2A degradation via proteasomes. Surprisingly, the absence of this E3 did not lead to generalized Pol II stalling and the subsequent generalized decrease of mRNA transcription but caused an enlarged Pol II pool size, which dysregulated 108 genes in NPCs, including some known to neural development. ARMC5 KO in the intestine downregulated FOHL1 expression, which was essential in folate absorption. Whole-exome sequencing of 511 myelomeningocele (MM) patients revealed nine highly deleterious mutations in the ARMC5 coding sequence. A significant deleterious mutation Arg429Cys found in MM patients drastically weakened the interaction between ARMC5 and POLR2A, supporting our hypothesis that such mutations in ARMC5 increased the NTD risks by compromising the POLR2A-specific E3 activity. Our results indicated that this novel ARMC5-CUL3-RBX1 E3 played a critical role in Pol II pool homeostasis, and ARMC5 mutation was a modifier of NTD risks in mice and humans.
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| Overall design |
Neural stem cell mRNA profiles from WT and Armc5(-/-) mice
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| Contributor(s) |
Luo H, Lao L, Wu J |
| Citation(s) |
38225631 |
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| Submission date |
Mar 22, 2021 |
| Last update date |
Jan 29, 2024 |
| Contact name |
Jiangping Wu |
| E-mail(s) |
jianping.wu@umontreal.ca
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| Organization name |
CR.CHUM
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| Street address |
900 Rue Saint Denis
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| City |
Montreal |
| ZIP/Postal code |
H2X0A9 |
| Country |
Canada |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA716311 |
| SRA |
SRP311672 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE169350_NSC_RNASeq_RawCounts_log2CPM_7SK.CAL.csv.gz |
5.6 Mb |
(ftp)(http) |
CSV |
| GSE169350_RAW.tar |
2.0 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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