{"doi":"10.1101/2021.12.11.472181","title":"Buffering of transcription rate by mRNA half-life is a conserved feature of Rett syndrome models","abstract":"Abstract 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 reinterpret 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 3’UTRs 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":222274,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":571802,"name":"Marat Mufteev","orcid":null,"position":1,"is_corresponding":false},{"id":581104,"name":"Kyoko E. Yuki","orcid":"0000-0003-0726-3914","position":2,"is_corresponding":false},{"id":823429,"name":"Ashrut Narula","orcid":"0000-0001-8140-635X","position":3,"is_corresponding":false},{"id":570793,"name":"Wei Wei","orcid":"0000-0002-2945-3543","position":4,"is_corresponding":false},{"id":571804,"name":"Alina Piekna","orcid":null,"position":5,"is_corresponding":false},{"id":823430,"name":"Jiajie Liu","orcid":"0009-0009-0850-7002","position":6,"is_corresponding":false},{"id":598502,"name":"Peter Pasceri","orcid":"0000-0002-2516-6694","position":7,"is_corresponding":false},{"id":563255,"name":"Olivia S. Rissland","orcid":"0000-0002-2619-6019","position":8,"is_corresponding":false},{"id":79291,"name":"Michael D. Wilson","orcid":"0000-0002-4015-3066","position":9,"is_corresponding":false},{"id":570864,"name":"James Ellis","orcid":"0000-0002-4400-0091","position":10,"is_corresponding":false},{"id":823428,"name":"Deivid C. Rodrigues","orcid":"0000-0001-5995-814X","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T23:54:03.549854Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}