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

Deivid C. Rodrigues, Marat Mufteev, Kyoko E. Yuki, Ashrut Narula, Wei Wei, Alina Piekna, Jiajie Liu, Peter Pasceri, Olivia S. Rissland, Michael D. Wilson and James Ellis ()
Additional contact information
Deivid C. Rodrigues: Hospital for Sick Children
Marat Mufteev: Hospital for Sick Children
Kyoko E. Yuki: Hospital for Sick Children
Ashrut Narula: University of Toronto
Wei Wei: Hospital for Sick Children
Alina Piekna: Hospital for Sick Children
Jiajie Liu: Hospital for Sick Children
Peter Pasceri: Hospital for Sick Children
Olivia S. Rissland: Hospital for Sick Children
Michael D. Wilson: University of Toronto
James Ellis: Hospital for Sick Children

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Transcriptional changes in Rett syndrome (RTT) are assumed to directly correlate with steady-state mRNA levels, but limited evidence in mice suggests that changes in transcription can be compensated by post-transcriptional regulation. We measure transcription rate and mRNA half-life changes in RTT patient neurons using RATEseq, and re-interpret nuclear and whole-cell RNAseq from Mecp2 mice. Genes are dysregulated by changing transcription rate or half-life and are buffered when both change. We utilized classifier models to predict the direction of transcription rate changes and find that combined frequencies of three dinucleotides are better predictors than CA and CG. MicroRNA and RNA-binding Protein (RBP) motifs are enriched in 3ʹUTRs of genes with half-life changes. Nuclear RBP motifs are enriched on buffered genes with increased transcription rate. We identify post-transcriptional mechanisms in humans and mice that alter half-life or buffer transcription rate changes when a transcriptional modulator gene is mutated in a neurodevelopmental disorder.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-37339-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37339-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-37339-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().