Nudt21 ablation in macrophages induces constitutive autophagy activation and diminishes inflammation in inflammatory diseases
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ABSTRACT:
PROVIDER: PRJNA1111003 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29006315_1.fastq.gz | Fastqsanger.gz | |||
| SRR29006315_2.fastq.gz | Fastqsanger.gz | |||
| SRR29006316_1.fastq.gz | Fastqsanger.gz | |||
| SRR29006316_2.fastq.gz | Fastqsanger.gz | |||
| SRR29006317_1.fastq.gz | Fastqsanger.gz |
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Project description:Macrophage hyperactivation is a hallmark of inflammatory diseases, yet the role of alternative polyadenylation (APA) in regulating innate immunity remains unclear. In this study, we demonstrate that Nudt21, a crucial RNA-binding component of the APA machinery, is significantly upregulated in various inflammatory settings. Utilizing myeloid-specific Nudt21-deficient mice, we reveal a protective effect of Nudt21 depletion against colitis and severe hyperinflammation, primarily through diminished production of proinflammatory cytokines. Notably, Nudt21 regulates the mRNA stability of key autophagy-related genes by mediating selective 3’UTR polyadenylation in activated macrophages. As a result, Nudt21-deficient macrophages display enhanced autophagic activity, which leads to reduced cytokine secretion.
2025-01-24 | GSE267291 | GEO
Project description:HCC is the third leading cause of cancer-related deaths worldwide. However, the molecular mechanisms underlying the progression of HCC is still largely elusive. NUDT21 (CFIm25) is an important mediator of 3′ UTR APA and demonstrates a causal relationship between alternative polyadenylation and cancer cell proliferation. Although the function of NUDT21 has been explored in glioblastoma tumor, the functional significance of NUDT21 in solid tumors is not well understood. In this study, we observed that NUDT21 is suppressed in human HCC tissues, compared to adjacent noncancerous tissues. In addition we found that the HCC patients with suppressed NUDT21 are statistically associated with poor outcomes. These observations suggest NUDT21 possibly functions as tumor suppressor in hepatocellular carcinoma (HCC).
2018-01-25 | E-MTAB-6368 | biostudies-arrayexpress
Project description:We identified LAMC1 as a critical NUDT21 target involved in several core glioma-driving signaling pathways. qRT-PCR analysis confirmed that NUDT21-knockdown in GBM cells resulted in the preferred usage of the proximal C/PAS of LAMC1. Furthermore, functional studies revealed that NUDT21-knockdown-induced 3’UTR shortening of LAMC1 was sufficient to induce translational gain, as LAMC1 was upregulated in these cells compared to their respective controls. Additionally, we demonstrated that primary glial cells recapitulated this phenomenon. We also further dissected the miRNA-mediated mechanism by which LAMC1 expression was regulated by showing that NUDT21 knockdown in glioma cells directed the 3’UTR shortening of LAMC1, removing binding sites for miR-124/506 and consequently inducing LAMC1 expression. Remarkably, we reported that the knockdown of NUDT21 significantly promoted GBM cell migration and that co-depletion of LAMC1 and NUDT21 abrogated this effect. Lastly, we observed that LAMC1 3’UTR shortening predicted poor prognosis of low- and high-grade glioma patients from The Cancer Genome Atlas.
2024-05-01 | GSE230769 | GEO
Project description:Cell fate transitions involve rapid changes of gene expression patterns and global chromatin remodeling, yet the underlying regulatory pathways remain incompletely understood. Here, we used transcription-factor induced reprogramming of somatic cells into pluripotent cells to screen for novel regulators of cell fate change. We identified the RNA processing factor Nudt21, a component of the pre-mRNA cleavage and polyadenylation complex, as a potent barrier to reprogramming. Importantly, suppression of Nudt21 not only enhanced the generation of induced pluripotent stem cells but also facilitated the conversion of fibroblasts into trophoblast stem cells and delayed the differentiation of myeloid precursor cells into macrophages, suggesting a broader role for Nudt21 in restricting cell fate change. Polyadenylation site sequencing (PAS-seq) revealed that Nudt21 directs differential polyadenylation of over 1,500 transcripts in cells acquiring pluripotency. While only a fraction of these transcripts changed expression at the protein level, this fraction was strongly enriched for chromatin regulators, including components of the PAF, polycomb, and trithorax complexes. Co-suppression analysis further suggests that these chromatin factors are largely responsible for Nudt21’s effect on reprogramming, providing a mechanistic basis for our observations. Collectively, our data uncover Nudt21 as a novel post-transcriptional regulator of mammalian cell fate and establish a direct, previously unappreciated link between alternative polyadenylation and chromatin signaling.
2017-10-26 | GSE99922 | GEO
Project description:Cell fate transitions involve rapid changes of gene expression patterns and global chromatin remodeling, yet the underlying regulatory pathways remain incompletely understood. Here, we used transcription-factor induced reprogramming of somatic cells into pluripotent cells to screen for novel regulators of cell fate change. We identified the RNA processing factor Nudt21, a component of the pre-mRNA cleavage and polyadenylation complex, as a potent barrier to reprogramming. Importantly, suppression of Nudt21 not only enhanced the generation of induced pluripotent stem cells but also facilitated the conversion of fibroblasts into trophoblast stem cells and delayed the differentiation of myeloid precursor cells into macrophages, suggesting a broader role for Nudt21 in restricting cell fate change. Polyadenylation site sequencing (PAS-seq) revealed that Nudt21 directs differential polyadenylation of over 1,500 transcripts in cells acquiring pluripotency. While only a fraction of these transcripts changed expression at the protein level, this fraction was strongly enriched for chromatin regulators, including components of the PAF, polycomb, and trithorax complexes. Co-suppression analysis further suggests that these chromatin factors are largely responsible for Nudt21’s effect on reprogramming, providing a mechanistic basis for our observations. Collectively, our data uncover Nudt21 as a novel post-transcriptional regulator of mammalian cell fate and establish a direct, previously unappreciated link between alternative polyadenylation and chromatin signaling.
2018-01-08 | PXD008078 | Pride
Project description:Cell fate transitions involve rapid changes of gene expression patterns and global chromatin remodeling, yet the underlying regulatory pathways remain incompletely understood. Here, we used transcription-factor induced reprogramming of somatic cells into pluripotent cells to screen for novel regulators of cell fate change. We identified the RNA processing factor Nudt21, a component of the pre-mRNA cleavage and polyadenylation complex, as a potent barrier to reprogramming. Importantly, suppression of Nudt21 not only enhanced the generation of induced pluripotent stem cells but also facilitated the conversion of fibroblasts into trophoblast stem cells and delayed the differentiation of myeloid precursor cells into macrophages, suggesting a broader role for Nudt21 in controlling cell fate change. Polyadenylation site sequencing (PAS-seq) revealed that Nudt21 directs differential polyadenylation of over 1,500 transcripts in cells acquiring pluripotency. While only a fraction of these transcripts changed expression at the protein level, this fraction was strongly enriched for chromatin regulators, including components of the PAF, Polycomb, and Trithorax complexes. Co-suppression analysis further suggests that these chromatin factors are potent mediators of reprogramming, providing a mechanistic basis for our observations. Collectively, our data uncover Nudt21 as a novel post-transcriptional regulator of mammalian cell fate and establish a direct, previously unappreciated link between alternative polyadenylation and chromatin signaling.
2017-10-26 | GSE104529 | GEO
Project description:To investigate the function of NUDT21 in the regulation of progression of colorectal cancer, we established HCT116 cell line in which each target gene has been knocked down by shRNA. We then performed gene expression profiling analysis using data obtained from RNA-seq of 4 different cells at two time points.
2024-01-01 | GSE223415 | GEO
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
Project description:Alternative polyadenylation modulates gene expresion via changing the length of 3'UTR. Among the complexes involving in APA, CFIm complex plays a central role in determining the usage of proximal PAS versus distal one. NUDT21, also named as CFIm25 and CPSF5, is the core component of CFIm complex. To date, except CPSF6 and CPSF7, there are few proteins reported to interact with NUDT21. In this project, the interactome of NUDT21 was identified by IP-MS.
2022-01-21 | PXD031134 |
Project description:CDK4 inhibition diminishes p53 activation by Mdm2-antagonists
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