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RNA half-life regulation reveals countercyclical regulation of buffered RNAs and RNAs undergoing changes in abundance

ABSTRACT: RNA half-life regulation reveals countercyclical regulation of buffered RNAs and RNAs undergoing changes in abundance

PROVIDER: PRJNA1167762 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30855156.fastq.gz	Fastqsanger.gz
	SRR30855157.fastq.gz	Fastqsanger.gz
	SRR30855158.fastq.gz	Fastqsanger.gz
	SRR30855159.fastq.gz	Fastqsanger.gz
	SRR30855160.fastq.gz	Fastqsanger.gz

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RNA half-life regulation reveals countercyclical regulation of buffered RNAs and RNAs undergoing changes in abundance

Project description:mRNA abundances are regulated by the opposing forces of transcription and decay, and yet how decay contributes to mRNA abundance regulation is largely unexplored. We addressed this question using genome-wide data on mRNA rates of abundance change, half-lives, and transcription rates of leaf cells responding to a transdifferentiation stimulusulus. Half-life regulation was common (22% of mRNAs underwent changes in half-life), but RNA abundance regulation by decay alone or by decay that supported transcriptional regulation was rare. Instead, most altered RNA half-lives opposed changes in transcription. Oppositionally regulated mRNAs were characterized by large changes in transcription and decay rates yet changes in mRNA abundances were either modest or undetectable, suggestive of RNA buffering. Oppositionally-regulated and buffered RNAs showed very similar dynamics, suggesting use of a common mechanism. The strongest contributions of RNA decay to RNA abundance regulation was in synergistically regulated transcripts, where rate changes in decay and transcription rates worked together to change RNA abundances.

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RNA half-life regulation reveals countercyclical regulation of buffered RNAs and RNAs undergoing changes in abundance [trim-Qfilt]

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Project description:RNA half-life regulation reveals countercyclical regulation of buffered RNAs and RNAs undergoing changes in abundance [trim-Qfilt]

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Buffering of transcription rate by mRNA half-life is a conserved feature of Rett syndrome models

Project description:Models of MECP2 dysfunction in Rett syndrome (RTT) assume that transcription rate changes directly correlate with altered steady-state mRNA levels. However, limited evidence suggests that transcription rate changes are buffered by poorly understood compensatory post-transcriptional mechanisms. Here we measure transcription rate and mRNA half-life changes in RTT patient neurons using RATE-seq, and re-interpret nuclear and whole-cell RNAseq from Mecp2 mice. Genes are dysregulated by changing transcription rate only or half-life only and are buffered when both are changed. We utilized classifier models to understand the direction of transcription rate changes based on gene-body DNA sequence, and combined frequencies of three dinucleotides were better predictors than contributions by CA and CG. MicroRNA and RNA-Binding Protein (RBP) motifs were enriched in 3ʹUTRs of genes with half-life changes. Motifs for nuclear localized RBPs were enriched on buffered genes with increased transcription rate. Our findings identify post-transcriptional mechanisms in humans and mice that alter half-life only or buffer transcription rate changes when a transcriptional modulator gene is mutated in a neurodevelopmental disorder.

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