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RNA Pol-II dependent transcription efficiency fine-tunes A-to-I editing levels

ABSTRACT: RNA Pol-II dependent transcription efficiency fine-tunes A-to-I editing levels

PROVIDER: PRJEB58992 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR12329600_1.fastq.gz	Fastqsanger.gz
	ERR12329600_2.fastq.gz	Fastqsanger.gz
	ERR12329700_1.fastq.gz	Fastqsanger.gz
	ERR12329700_2.fastq.gz	Fastqsanger.gz
	ERR12329601_1.fastq.gz	Fastqsanger.gz

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RNA Pol II-dependent transcription efficiency fine-tunes A-to-I editing levels.

Project description:A-to-I RNA editing is a widespread epitranscriptomic phenomenon leading to the conversion of adenosines to inosines, which are primarily interpreted as guanosines by cellular machines. Consequently, A-to-I editing can alter splicing or lead to recoding of transcripts. As misregulation of editing can cause a variety of human diseases, A-to-I editing requires tight regulation of the extent of deamination, particularly in protein-coding regions. The bulk of A-to-I editing occurs cotranscriptionally. Thus, we studied A-to-I editing regulation in the context of transcription and pre-mRNA processing. We show that stimulation of transcription impacts editing levels. Activation of the transcription factor MYC leads to an up-regulation of A-to-I editing, particularly in transcripts that are suppressed upon MYC activation. Moreover, low pre-mRNA synthesis rates and low pre-mRNA expression levels support high levels of editing. We also show that editing levels greatly differ between nascent pre-mRNA and mRNA in a cellular system, as well as in mouse tissues. Editing levels can increase or decrease from pre-mRNA to mRNA and can vary across editing targets and across tissues, showing that pre-mRNA processing is an important layer of editing regulation. Several lines of evidence suggest that the differences emerge during pre-mRNA splicing. Moreover, actinomycin D treatment of primary neuronal cells and editing level analysis suggests that regulation of editing levels also depends on transcription.

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