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Comparative analysis between single-cell RNA-seq and single-molecule RNA FISH indicates that the pyrimidine nucleobase idoxuridine (IdU) globally amplifies transcriptional noise

ABSTRACT: Comparative analysis between single-cell RNA-seq and single-molecule RNA FISH indicates that the pyrimidine nucleobase idoxuridine (IdU) globally amplifies transcriptional noise

PROVIDER: PRJNA1096246 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28553692_1.fastq.gz	Fastqsanger.gz
	SRR28553692_2.fastq.gz	Fastqsanger.gz
	SRR28553693_1.fastq.gz	Fastqsanger.gz
	SRR28553693_2.fastq.gz	Fastqsanger.gz
	SRR28553694_1.fastq.gz	Fastqsanger.gz

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Comparative analysis between single-cell RNA-seq and single-molecule RNA FISH indicates that the pyrimidine nucleobase idoxuridine (IdU) globally amplifies transcriptional noise

Project description:Stochastic fluctuations (noise) in transcription generate substantial cell-to-cell variability, but the physiological roles of noise have remained difficult to determine in the absence of generalized noise-modulation approaches. Previous single-cell RNA-sequencing (scRNA-seq) suggested that the pyrimidine-base analog (5′-iodo-2′-deoxyuridine, IdU) could generally amplify noise without substantially altering mean-expression levels but scRNA-seq technical drawbacks potentially obscured the penetrance of IdU-induced transcriptional noise amplification. Here we quantify global-vs.-partial penetrance of IdU-induced noise amplification by assessing scRNA-seq data using numerous normalization algorithms and complement our previous results with data from Human Jurkat T Lymphocytes, including two biological replicates to allow rigorous statistical analysis. Collectively, this analysis indicates which scRNA-seq algorithms are appropriate for quantifying noise and argues that IdU is a globally penetrant noise-enhancer molecule that could enable investigations of the physiological impacts of transcriptional noise in various cell types and organisms.

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Major roles of cyclobutane pyrimidine dimers, nucleotide excision repair and ATR in the alternative splicing response to UV irradiation

Project description:Alternative splicing (AS) is the main process that amplifies DNA information and is a crucial target of signaling cascades resulting from UV irradiation of human cells. The specific impact of UV-induced cyclobutane pyrimidine dimers (CPDs) at the transcriptional and AS levels has not been addressed. By using a CPD photolyase, a flavoenzyme that directly reverts CPDs, we analyze the contribution of this lesion to the expression program in human keratinocytes.

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Nucleobase adducts bind MR1 and stimulate MR1-restricted T cells

Project description:MR1T cells are a recently discovered class of T cells that recognize antigens presented by the MHC-I–related molecule MR1 in the absence of microbial infection. The nature of the self-antigens that stimulate MR1T cells remains unclear, hampering our understanding of their physiological role and therapeutic potential. By combining genetic, pharmacological, and biochemical approaches, we found that carbonyl stress and changes in nucleobase metabolism in target cells promote MR1T cell activation. Stimulatory compounds formed by carbonyl adducts of nucleobases were detected within MR1 molecules produced by tumor cells and their abundance and antigenicity were enhanced by drugs that induce carbonyl accumulation. Our data reveal carbonyl nucleobase adducts as MR1T cell antigens. Recognizing cells under carbonyl stress allows MR1T cells to monitor cellular metabolic changes with physiological and therapeutic implications.

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Cellular pyrimidine imbalance triggers mitochondrial DNA-dependent innate immunity [A33_OE_RNA-seq]

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