Reference - PMID:38133430 - Genetic suppressor screen identifies Tgp1 (glycerophosphocholine transporter), Kcs1 (IP 6 kinase), and Plc1 (phospholipase C) as determinants of inositol pyrophosphate toxicosis in fission yeast.
Reference summary
- PubMed ID
- PMID:38133430
- Title
- Genetic suppressor screen identifies Tgp1 (glycerophosphocholine transporter), Kcs1 (IP 6 kinase), and Plc1 (phospholipase C) as determinants of inositol pyrophosphate toxicosis in fission yeast.
- Authors
- Bednor L, Sanchez AM, Garg A, Shuman S, Schwer B
- Citation
- mBio 2023 Dec 22;:e0306223
- Publication year
- 2023
- 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 >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 .
