{"doi":"10.1101/2025.05.08.652725","title":"P-body factors Ddx6 and Ddx61 support development in mRNA-decay deficient <i>pnrc2</i> mutants","abstract":"Somitogenesis is controlled by the segmentation clock, a molecular oscillator that controls periodic gene expression in unsegmented mesoderm and is regulated by a negative feedback loop driven by Hes/Her transcriptional repressors. In zebrafish, Pnrc2 is required for decay of her1 transcript and additional oscillatory gene transcripts. Despite accumulation of numerous mRNAs including those encoding developmental regulators, overt embryonic phenotypes are absent in pnrc2 mutants. Our previous work suggested that accumulated mRNAs are not translated in pnrc2 mutants, though the underlying mechanism(s) was unknown. We show here that many overexpressed transcripts in pnrc2 mutants have shortened poly(A) tails and are disengaged from ribosomes, and that deadenylation inhibition leads to somite defects in pnrc2 mutants. Transcripts encoding the P-body protein, Ddx61, are both overexpressed and engaged with ribosomes in pnrc2 mutants, leading to an increase in Ddx61 protein that may compensate against the negative effects of transcript accumulation. Co-depletion of Ddx61 and Ddx6 in pnrc2 mutants increases her1 accumulation and leads to pleiotropic defects. Together, our results show that multiple post-transcriptional mechanisms ensure proper translation when mRNA decay is inhibited.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":565940,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9434,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1469805,"name":"Monica C. Blatnik","orcid":null,"position":1,"is_corresponding":false},{"id":1469806,"name":"Clare C Austin","orcid":null,"position":2,"is_corresponding":false},{"id":1469807,"name":"Kathryn G Thompson","orcid":null,"position":3,"is_corresponding":false},{"id":1469808,"name":"Danielle M Pvirre","orcid":null,"position":4,"is_corresponding":false},{"id":1469809,"name":"Ryan Denniston","orcid":null,"position":5,"is_corresponding":false},{"id":1469810,"name":"Angelina Morgan","orcid":null,"position":6,"is_corresponding":false},{"id":955799,"name":"Michael G. Kearse","orcid":"0000-0002-7025-8803","position":7,"is_corresponding":false},{"id":392231,"name":"Sharon L. Amacher","orcid":"0000-0002-0640-5071","position":8,"is_corresponding":false},{"id":392228,"name":"Thomas L. Gallagher","orcid":"0000-0003-1461-8496","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:56:32.546082Z","pmid":"40463158","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":[]}