{"doi":"10.1016/j.xgen.2024.100563","title":"Lineage-specific splicing regulation of MAPT gene in the primate brain","abstract":"Divergence of precursor messenger RNA (pre-mRNA) alternative splicing (AS) is widespread in mammals, including primates, but the underlying mechanisms and functional impact are poorly understood. Here, we modeled cassette exon inclusion in primate brains as a quantitative trait and identified 1,170 (∼3%) exons with lineage-specific splicing shifts under stabilizing selection. Among them, microtubule-associated protein tau (MAPT) exons 2 and 10 underwent anticorrelated, two-step evolutionary shifts in the catarrhine and hominoid lineages, leading to their present inclusion levels in humans. The developmental-stage-specific divergence of exon 10 splicing, whose dysregulation can cause frontotemporal lobar degeneration (FTLD), is mediated by divergent distal intronic MBNL-binding sites. Competitive binding of these sites by CRISPR-dCas13d/gRNAs effectively reduces exon 10 inclusion, potentially providing a therapeutically compatible approach to modulate tau isoform expression. Our data suggest adaptation of MAPT function and, more generally, a role for AS in the evolutionary expansion of the primate brain.","journal":"Cell Genomics","year":2024,"id":444696,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":843673,"name":"Suying Bao","orcid":"0000-0002-6220-0257","position":1,"is_corresponding":false},{"id":970289,"name":"Xiaojian Wang","orcid":"0000-0002-1502-8781","position":2,"is_corresponding":false},{"id":1260637,"name":"Brittany L. Phillips","orcid":null,"position":3,"is_corresponding":false},{"id":909174,"name":"Yow-Tyng Yeh","orcid":"0000-0002-3865-8102","position":4,"is_corresponding":false},{"id":1260162,"name":"Sebastien M. Weyn‐Vanhentenryck","orcid":"0000-0002-5750-0319","position":5,"is_corresponding":false},{"id":311456,"name":"Maurice S. Swanson","orcid":"0000-0001-6245-5367","position":6,"is_corresponding":false},{"id":406994,"name":"Chaolin Zhang","orcid":"0000-0002-8310-7537","position":7,"is_corresponding":false},{"id":291012,"name":"Yocelyn Recinos","orcid":"0000-0002-7377-8660","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:01:37.886033Z","pmid":"38772368","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":[]}