{"doi":"10.1128/mbio.03062-23","title":"Genetic suppressor screen identifies Tgp1 (glycerophosphocholine transporter), Kcs1 (IP <sub>6</sub> kinase), and Plc1 (phospholipase C) as determinants of inositol pyrophosphate toxicosis in fission yeast","abstract":"The inositol pyrophosphate metabolite 1,5-IP 8 governs repression of fission yeast phosphate homeostasis genes pho1 , pho84 , and tgp1 by lncRNA-mediated transcriptional interference. Asp1 pyrophosphatase mutations that increase IP 8 levels elicit precocious lncRNA termination, leading to derepression of the PHO genes. Deletions of the Asp1 pyrophosphatase domain result in growth impairment or lethality via IP 8 agonism of transcription termination. It was assumed that IP 8 toxicity ensues from dysregulation of essential genes. In this study, a suppressor screen revealed that IP 8 toxicosis of Asp1 pyrophosphatase mutants is caused by: (i) a &gt;40-fold increase in the expression of the inessential tgp1 gene encoding a glycerophosphodiester transporter and (ii) the presence of glycerophosphocholine in the growth medium. The suppressor screen yielded missense mutations in two upstream enzymes of inositol polyphosphate metabolism: the phospholipase C enzyme Plc1 that generates IP 3 and the essential Kcs1 kinase that converts IP 6 to 5-IP 7 , the immediate precursor of IP 8 .","journal":"mBio","year":2023,"id":352174,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"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":409032,"name":"Ana M. Sánchez","orcid":"0000-0002-9119-7624","position":1,"is_corresponding":false},{"id":409033,"name":"Angad Garg","orcid":"0000-0003-4494-6386","position":2,"is_corresponding":false},{"id":409034,"name":"Stewart Shuman","orcid":"0000-0001-5034-6438","position":3,"is_corresponding":false},{"id":409035,"name":"Beate Schwer","orcid":"0000-0002-3824-9819","position":4,"is_corresponding":false},{"id":1097721,"name":"Lauren Bednor","orcid":"0000-0001-5136-470X","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:12:50.107998Z","pmid":"38133430","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":[]}