{"doi":"10.1261/rna.079595.123","title":"Duf89 abets lncRNA control of fission yeast phosphate homeostasis via its antagonism of precocious lncRNA transcription termination","abstract":"Fission yeast phosphate homeostasis gene pho1 is actively repressed during growth in phosphate-rich medium by transcription in cis of a long noncoding (lnc) RNA from the 5′ flanking prt(nc-pho1) gene. Pho1 expression is: (i) derepressed by genetic maneuvers that favor precocious lncRNA 3′-processing and termination, in response to DSR and PAS signals in prt ; and (ii) hyperrepressed in genetic backgrounds that dampen 3′-processing/termination efficiency. Governors of 3′-processing/termination include the RNA polymerase CTD code, the CPF (cleavage and polyadenylation factor) complex, termination factors Seb1 and Rhn1, and the inositol pyrophosphate signaling molecule 1,5-IP 8 . Here, we present genetic and biochemical evidence that fission yeast Duf89, a metal-dependent phosphatase/pyrophosphatase, is an antagonist of precocious 3′-processing/termination. We show that derepression of pho1 in duf89 Δ cells correlates with squelching the production of full-length prt lncRNA and is erased or attenuated by: (i) DSR/PAS mutations in prt ; (ii) loss-of-function mutations in components of the 3′-processing and termination machinery; (iii) elimination of the CTD Thr4-PO 4 mark; (iv) interdicting CTD prolyl isomerization by Pin1; (v) inactivating the Asp1 kinase that synthesizes IP 8 ; and (vi) loss of the putative IP 8 sensor Spx1. The findings that duf89 Δ is synthetically lethal with pho1 -derepressive mutations CTD-S7A and aps1 Δ—and that this lethality is rescued by CTD-T4A , CPF/Rhn1/Pin1 mutations, and spx1 Δ—implicate Duf89 more broadly as a collaborator in cotranscriptional regulation of essential fission yeast genes. The duf89-D252A mutation, which abolishes Duf89 phosphohydrolase activity, phenocopied duf89 + , signifying that duf89 Δ phenotypes are a consequence of Duf89 protein absence, not absence of Duf89 catalysis.","journal":"RNA","year":2023,"id":372338,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9433,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":409033,"name":"Angad Garg","orcid":"0000-0003-4494-6386","position":1,"is_corresponding":false},{"id":409035,"name":"Beate Schwer","orcid":"0000-0002-3824-9819","position":2,"is_corresponding":false},{"id":409034,"name":"Stewart Shuman","orcid":"0000-0001-5034-6438","position":3,"is_corresponding":false},{"id":409032,"name":"Ana M. Sánchez","orcid":"0000-0002-9119-7624","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T01:15:54.000926Z","pmid":"36882296","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":[]}