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Induction of a transcriptional adaptation response by RNA destabilization events [dst175]

ABSTRACT: Transcriptional adaptation (TA) is a cellular process whereby mRNA-destabilizing mutations lead to the transcriptional upregulation of so-called adapting genes. The nature of the TA-triggering factor(s) remains unclear. Here, we first generated Cas9-induced mutations in mouse Actg1, including an mRNA-destabilizing allele and an RNA-less allele. We find in the Actg1 mRNA-destabilizing allele, higher levels of Actg2 mRNA as well as increased chromatin accessibility at the Actg2 locus compared with wild-type and the RNA-less allele. Notably, Cas13d experiments show that Actg1 mRNA cleavage, but not Actg1 pre-mRNA cleavage, also triggers Actg2 upregulation; however, this upregulation is not associated with increased chromatin accessibility at the Actg2 locus. Furthermore, time course experiments show that increased Actg2 expression persists even after Actg1 mRNA degradation by Cas13d ceases. Together, our data highlight the importance of cytoplasmic mRNA degradation as a trigger for the TA response and suggest that chromatin remodeling is not necessary for TA.

ORGANISM(S): Mus musculus

PROVIDER: GSE286097 | GEO | 2025/03/17

REPOSITORIES: GEO

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Induction of a transcriptional adaptation response via perturbations at the DNA and RNA levels [dst233]

Project description:Transcriptional adaptation (TA) is a cellular process whereby mRNA-destabilizing mutations lead to the transcriptional upregulation of so-called adapting genes. The nature of the TA-triggering factor(s) remains unclear. Here, we first generated Cas9-induced mutations in mouse Actg1, including an mRNA-destabilizing allele and an RNA-less allele. We find in the Actg1 mRNA-destabilizing allele, higher levels of Actg2 mRNA as well as increased chromatin accessibility at the Actg2 locus compared with wild-type and the RNA-less allele. Notably, Cas13d experiments show that Actg1 mRNA cleavage, but not Actg1 pre-mRNA cleavage, also triggers Actg2 upregulation; however, this upregulation is not associated with increased chromatin accessibility at the Actg2 locus. Furthermore, time course experiments show that increased Actg2 expression persists even after Actg1 mRNA degradation by Cas13d ceases. Together, our data highlight the importance of cytoplasmic mRNA degradation as a trigger for the TA response and suggest that chromatin remodeling is not necessary for TA.

2025-03-17 | GSE255120 | GEO

Induction of a transcriptional adaptation response by RNA destabilization events [dst278]

Project description:Transcriptional adaptation (TA) is a cellular process whereby mRNA-destabilizing mutations lead to the transcriptional upregulation of so-called adapting genes. The nature of the TA-triggering factor(s) remains unclear, namely whether an mRNA-borne premature termination codon (PTC) or the subsequent mRNA degradation process, and/or its products, elicits TA. Here, we first established two perturbations leading to mRNA destabilization for mouse Actg1: a Cas9-induced mutation that leads to a PTC, and Cas13d-mediated mRNA cleavage. We find that both perturbations are effective in degrading Actg1 mRNA and upregulating Actg2. Notably, increased chromatin accessibility at the Actg2 locus was observed only in the Cas9-induced mutant allele but not in the Cas13d-targeted cells, suggesting that chromatin remodeling is not required for Actg2 upregulation. We further show that ribozyme-mediated Actg1 pre-mRNA cleavage also leads to a robust upregulation of Actg2. Together, these data highlight the critical role of RNA destabilization events as a trigger for TA.

2025-03-17 | GSE282000 | GEO

RNA-Targeting CRISPR/Cas13d System Alleviates Disease-Related Phenotypes in Pre-clinical Models of Huntington’s Disease (Human).

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RNA-Targeting CRISPR/Cas13d System Alleviates Disease-Related Phenotypes in Pre-clinical Models of Huntington’s Disease (Mouse).

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Negative autoregulation mitigates collateral RNase activity of repeat-targeting CRISPR-Cas13d in mammalian cells

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Nicotiana tabacum degradome analysis using high definition adapters proves an efficient targeting method against the Tomato leaf curl New Delhi virus using artificial ta-siRNAs [PARE]

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Nicotiana tabacum degradome analysis using high definition adapters proves an efficient targeting method against the Tomato leaf curl New Delhi virus using artificial ta-siRNAs [sRNA-seq]

2019-11-08 | GSE85816 | GEO

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