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Buffering of transcription rate by mRNA half-life is a conserved feature of Rett syndrome models
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 p...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076348/ https://www.ncbi.nlm.nih.gov/pubmed/37019888 http://dx.doi.org/10.1038/s41467-023-37339-6 |
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author | Rodrigues, Deivid C. Mufteev, Marat Yuki, Kyoko E. Narula, Ashrut Wei, Wei Piekna, Alina Liu, Jiajie Pasceri, Peter Rissland, Olivia S. Wilson, Michael D. Ellis, James |
author_facet | Rodrigues, Deivid C. Mufteev, Marat Yuki, Kyoko E. Narula, Ashrut Wei, Wei Piekna, Alina Liu, Jiajie Pasceri, Peter Rissland, Olivia S. Wilson, Michael D. Ellis, James |
author_sort | Rodrigues, Deivid C. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10076348 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-100763482023-04-07 Buffering of transcription rate by mRNA half-life is a conserved feature of Rett syndrome models Rodrigues, Deivid C. Mufteev, Marat Yuki, Kyoko E. Narula, Ashrut Wei, Wei Piekna, Alina Liu, Jiajie Pasceri, Peter Rissland, Olivia S. Wilson, Michael D. Ellis, James Nat Commun Article 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. Nature Publishing Group UK 2023-04-05 /pmc/articles/PMC10076348/ /pubmed/37019888 http://dx.doi.org/10.1038/s41467-023-37339-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Rodrigues, Deivid C. Mufteev, Marat Yuki, Kyoko E. Narula, Ashrut Wei, Wei Piekna, Alina Liu, Jiajie Pasceri, Peter Rissland, Olivia S. Wilson, Michael D. Ellis, James Buffering of transcription rate by mRNA half-life is a conserved feature of Rett syndrome models |
title | Buffering of transcription rate by mRNA half-life is a conserved feature of Rett syndrome models |
title_full | Buffering of transcription rate by mRNA half-life is a conserved feature of Rett syndrome models |
title_fullStr | Buffering of transcription rate by mRNA half-life is a conserved feature of Rett syndrome models |
title_full_unstemmed | Buffering of transcription rate by mRNA half-life is a conserved feature of Rett syndrome models |
title_short | Buffering of transcription rate by mRNA half-life is a conserved feature of Rett syndrome models |
title_sort | buffering of transcription rate by mrna half-life is a conserved feature of rett syndrome models |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076348/ https://www.ncbi.nlm.nih.gov/pubmed/37019888 http://dx.doi.org/10.1038/s41467-023-37339-6 |
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