Omics · study · 2026
Dynamic phosphorylation of DGCR8 regulates embryonic stem cell differentiation and Microprocessor function
Listed in NCBI GEO
The Microprocessor complex, minimally composed of DROSHA and DGCR8, is ubiquitously required for microRNA biogenesis.
Description
It also regulates the balance between pluripotency and differentiation through mRNA alternative splicing and mRNA cleavage. However, how these various activities are controlled remains unclear.
Both DROSHA and DGCR8 are phosphoproteins, and phosphorylation has been reported to influence their molecular functions. In this study, we identified residues in DGCR8 by mass spectrometry that are differentially phosphorylated between mouse embryonic stem cells (mESCs) and mESC-derived neuronal cells. This included S95, which was enriched in the stem cell state, and S238, which was enriched in differentiated cells.
Read the rest (3 more)
By means of CRISPR/Cas9-mediated genome editing of the endogenous Dgcr8 gene, we generated DGCR8 phospho-deficient mESC mutants. Despite the disruption of these phospho-sites, the mutants retained their mESC phenotype and remained partially capable of undergoing neuronal and spontaneous differentiation. However, the S95A mutation altered miRNA profiles, Chpf2 mRNA cleavage, and Tcf7l1 alternative splicing in mESCs.
Both mutants exhibited altered neuronal and spontaneous differentiation outcomes. During neuronal differentiation, the S238A mutant displayed elevated mRNA expression of neuronal progenitor markers even after 10 days, while both mutants failed to generate cardiomyocytes in embryoid body differentiation cultures. Furthermore, MEK1/2 inhibition with a highly selective inhibitor partially phenocopied the transcriptional effects of S95A in mESCs, suggesting ERK/MAPK signaling may contribute to the regulation of DGCR8 phosphorylation.
Our results demonstrated that phosphorylation of specific residues in DGCR8 modulates Microprocessor-dependent processes and influences differentiation outcomes, establishing DGCR8 phosphorylation as an important regulatory mechanism in the regulation of Microprocessor activity, especially for stem cell differentiation.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336265 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE336265 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1481178 ncbi.nlm.nih.gov/bioproject/PRJNA1481178 ↗
project · from NCBI GEO
Topics
- Stated by source
- Mus musculus · Non-coding RNA profiling by high throughput sequencing
- From keywords
- Life Sciences
- Inferred from text
- Mass spectrometry 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE336265 | 7 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:non-coding-rna-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:mass-spectrometry | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |