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Sites of transcription initiation drive mRNA isoform selection [cDNANanopore]

ABSTRACT: Sites of transcription initiation drive mRNA isoform selection [cDNANanopore]

PROVIDER: PRJNA841496 | ENA |

REPOSITORIES: ENA

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Dataset's files

Source:

			Action	DRS
		Other
	SRR19355626_1.fastq.gz	Fastqsanger.gz
	SRR19355627_1.fastq.gz	Fastqsanger.gz
	SRR19355628_1.fastq.gz	Fastqsanger.gz
	SRR19355629_1.fastq.gz	Fastqsanger.gz

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Project description:The generation of distinct messenger RNA isoforms through alternative RNA processing influences the expression and function of genes, often in a cell-type specific manner. Here, we assess the regulatory relationships between transcription initiation, alternative splicing, and 3ʹ end site selection. Applying multiple long-read-sequencing approaches to obtain an assembly accurately representing even the longest transcripts from end to end, we quantify mRNA isoform choice in Drosophila and human tissues, including the transcriptionally complex nervous system. We find that in Drosophila brains as well as in human cerebral organoids, 3ʹ end site choice is globally influenced by the site of transcription initiation. “Dominant promoters”, characterized by specific epigenetic signatures including p300/CBP binding, impose a transcriptional constraint to define splice and polyadenylation variants. In vivo deletion or overexpression of dominant promoters as well as CBP/p300 loss disrupted the 3ʹ end expression landscape. Our study demonstrates the crucial impact of TSS choice on the regulation of transcript diversity and tissue identity.

2023-05-10 | GSE221324 | GEO

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