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Intron detention tightly regulates the stemness/differentiation switch in the adult neurogenic niche

ABSTRACT: Intron detention tightly regulates the stemness/differentiation switch in the adult neurogenic niche

PROVIDER: PRJNA749595 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15242843_1.fastq.gz	Fastqsanger.gz
	SRR15242843_2.fastq.gz	Fastqsanger.gz
	SRR15242844_1.fastq.gz	Fastqsanger.gz
	SRR15242844_2.fastq.gz	Fastqsanger.gz
	SRR15242845_1.fastq.gz	Fastqsanger.gz

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Intron detention tightly regulates the stemness/differentiation switch in the adult neurogenic niche.

Project description:The adult mammalian brain retains some capacity to replenish neurons and glia, holding promise for brain regeneration. Thus, understanding the mechanisms controlling adult neural stem cell (NSC) differentiation is crucial. Paradoxically, adult NSCs in the subependymal zone transcribe genes associated with both multipotency maintenance and neural differentiation, but the mechanism that prevents conflicts in fate decisions due to these opposing transcriptional programmes is unknown. Here we describe intron detention as such control mechanism. In NSCs, while multiple mRNAs from stemness genes are spliced and exported to the cytoplasm, transcripts from differentiation genes remain unspliced and detained in the nucleus, and the opposite is true under neural differentiation conditions. We also show that m6A methylation is the mechanism that releases intron detention and triggers nuclear export, enabling rapid and synchronized responses. m6A RNA methylation operates as an on/off switch for transcripts with antagonistic functions, tightly controlling the timing of NSCs commitment to differentiation.

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SFSWAP is a negative regulator of OGT intron detention and global pre-mRNA splicing [CRISPR]

Project description:In this study, we identified SFSWAP as a negative regulator of O-GlcNAc transferase (OGT) intron 4 detention and global pre-mRNA splicing. To do this, we performed CRISPR knockout screens using the Brunello knockout library on Thiamet G (TG)-treated HCT116 cells containing an O-GlcNAc responsive GFP reporter (GFP-β-OGT) integrated at the AAVS1 locus. Knockout of negative regulatory factors which regulate OGT intron 4 detention lead to increased GFP expression. Using replicate screens and further biochemical validation, we identified SFSWAP as one of the top hits affecting OGT intron 4 detention.

2024-10-16 | GSE277949 | GEO

Intron detention tightly regulates the stemness/differentiation switch in the adult neurogenic niche

Project description:The goal of this study is to analyze the changes in the transcriptional profile at the first stages of neural stem cell (NSC) differentiation.

2024-02-14 | GSE180806 | GEO

CRISPR screen identifies NUDT21 as a regulator of intron detention of the SAM synthetase MAT2A RNA

Project description:The only S-adenosymethionine (SAM) synthetase expressed in most human cells, MAT2A, is regulated by intron detention. Using a GFP fusion reporter, we conducted a CRISPR screen to identify regulators of this alternative splicing event. The screen identified METTL16, a known regulator of this process, and NUDT21. NUDT21 encodes the CFIm25 protein a member of the CFIm complex involved in alternative polyadenylation. Validation and follow-up studies support the idea that CFIm25 and the larger CFIm complex plays an unanticipated role in splicing of the MAT2A detained intron.

2021-05-04 | GSE172217 | GEO

NUDT21 regulates intron detention of the SAM synthetase MAT2A RNA

Project description:NUDT21 regulates intron detention of the SAM synthetase MAT2A RNA

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SFSWAP is a negative regulator of OGT intron detention and global pre-mRNA splicing [RNA-seq I]

Project description:In this study, we identified SFSWAP as a negative regulator of O-GlcNAc transferase (OGT) intron 4 detention and global pre-mRNA splicing using a CRISPR knockout screen in an O-GlcNAc responsive GFP reporter cell line. In order to characterize the functions of the protein, we performed siRNA mediated knockdown of SFSWAP followed by RNA-seq analysis under untreated conditions. Alternate splicing analysis using rMATS (and other tools) revealed enhanced splicing of retained introns and increased inclusion of cassette exons upon knockdown of SFSWAP, supporting an inhibitory role for SFSWAP in splicing.

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SFSWAP is a negative regulator of OGT intron detention and global pre-mRNA splicing [RNA-seq II]

Project description:In this study, we identified SFSWAP as a negative regulator of O-GlcNAc transferase (OGT) intron 4 detention and global pre-mRNA splicing using a CRISPR knockout screen in an O-GlcNAc responsive GFP reporter cell line. In order to characterize the functions of the protein, we performed siRNA mediated knockdown of SFSWAP followed by RNA-seq analysis under TG-treated conditions. In addition, we performed the same analysis under UPF1 knockdown conditions to stabilize NMD targeted transcripts. Alternate splicing analysis using rMATS (and other tools) revealed enhanced splicing of retained introns and increased inclusion of cassette exons upon knockdown of SFSWAP, supporting an inhibitory role for SFSWAP in splicing.

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Type I and II PRMTs Inversely Regulate Post-Transcriptional Intron Detention through

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SFSWAP is a negative regulator of OGT intron detention and global pre-mRNA splicing [CRISPR]

Project description:SFSWAP is a negative regulator of OGT intron detention and global pre-mRNA splicing [CRISPR]

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