{"doi":"10.7554/elife.71892","title":"FMRP regulates mRNAs encoding distinct functions in the cell body and dendrites of CA1 pyramidal neurons","abstract":"Neurons rely on translation of synaptic mRNAs in order to generate activity-dependent changes in plasticity. Here, we develop a strategy combining compartment-specific crosslinking immunoprecipitation (CLIP) and translating ribosome affinity purification (TRAP) in conditionally tagged mice to precisely define the ribosome-bound dendritic transcriptome of CA1 pyramidal neurons. We identify CA1 dendritic transcripts with differentially localized mRNA isoforms generated by alternative polyadenylation and alternative splicing, including many that have altered protein-coding capacity. Among dendritic mRNAs, FMRP targets were found to be overrepresented. Cell-type-specific FMRP-CLIP and TRAP in microdissected CA1 neuropil revealed 383 dendritic FMRP targets and suggests that FMRP differentially regulates functionally distinct modules in CA1 dendrites and cell bodies. FMRP regulates ~15-20% of mRNAs encoding synaptic functions and 10% of chromatin modulators, in the dendrite and cell body, respectively. In the absence of FMRP, dendritic FMRP targets had increased ribosome association, consistent with a function for FMRP in synaptic translational repression. Conversely, downregulation of FMRP targets involved in chromatin regulation in cell bodies suggests a role for FMRP in stabilizing mRNAs containing stalled ribosomes in this compartment. Together, the data support a model in which FMRP regulates the translation and expression of synaptic and nuclear proteins within different compartments of a single neuronal cell type.","journal":"eLife","year":2021,"id":155216,"datarank":1.4416187839486407,"base_score":4.110873864173311,"endowment":4.110873864173311,"self_citation_contribution":0.6166310796259968,"citation_network_contribution":0.8249877043226438,"self_endowment_contribution":0.6166310796259968,"citer_contribution":0.8249877043226438,"corpus_percentile":null,"corpus_rank":null,"citation_count":60,"citer_count":57,"citers_with_citation_signal":41,"citers_with_endowment":41,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9504,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE174303","GSE96722","GSE84786","GSE69711","GSE94054","GSE127847"]},"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":94647,"name":"Kirsty Sawicka","orcid":"0000-0003-4195-6327","position":1,"is_corresponding":false},{"id":657820,"name":"Kevin Mora","orcid":null,"position":2,"is_corresponding":false},{"id":245572,"name":"John J. Fak","orcid":"0000-0002-7237-4699","position":3,"is_corresponding":false},{"id":275600,"name":"Jin Joo Kang","orcid":"0000-0002-4249-9570","position":4,"is_corresponding":false},{"id":657821,"name":"Paula Cutrim","orcid":null,"position":5,"is_corresponding":false},{"id":657822,"name":"Katarzyna Cialowicz","orcid":null,"position":6,"is_corresponding":false},{"id":551529,"name":"Thomas S. Carroll","orcid":null,"position":7,"is_corresponding":false},{"id":245576,"name":"Robert B. Darnell","orcid":"0000-0002-5134-8088","position":8,"is_corresponding":false},{"id":245575,"name":"Caryn Hale","orcid":"0000-0002-2860-0994","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-18T23:43:59.154159Z","pmid":"34939924","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":[]}