Cyclophilin A is localized to the nucleus and controls meiosis in Saccharomyces cerevisiae.
Cyclophilin A is conserved from yeast to humans and mediates the ability of cyclosporine to perturb signal transduction cascades via inhibition of calcineurin. Cyclophilin A also catalyzes cis-trans peptidyl-prolyl isomerization during protein folding or conformational changes; however, cyclophilin A is not essential in yeast or human cells, and the true biological functions of this highly conserved enzyme have remained enigmatic. In Saccharomyces cerevisiae, cyclophilin A becomes essential in cells compromised for the nuclear prolyl-isomerase Ess1, and cyclophilin A physically interacts with two nuclear histone deacetylase complexes, Sin3-Rpd3 and Set3C, which both control meiosis. Here we show that cyclophilin A is localized to the nucleus in yeast cells and governs the meiotic gene program to promote efficient sporulation. The prolyl-isomerase activity of cyclophilin A is required for this meiotic function. We document that cyclophilin A physically associates with the Set3C histone deacetylase and analyze in detail the structure of this protein-protein complex. Genetic studies support a model in which cyclophilin A controls meiosis via Set3C and an additional target. Our findings reveal a novel nuclear role for cyclophilin A in governing the transcriptional program required for the vegetative to meiotic developmental switch in budding yeast.
Arévalo-Rodríguez
Miguel
M
Department of Molecular Genetics and Microbiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
Heitman
Joseph
J
D015152:Blotting, Northern; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism*; D021984:Cyclophilin A / Q000096:biosynthesis*; D003593:Cytoplasm / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D047468:Immunoprecipitation; D008540:Meiosis; D008954:Models, Biological; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009841:Oligonucleotides / Q000737:chemistry; D019696:Peptidylprolyl Isomerase / Q000378:metabolism / Q000502:physiology; D010957:Plasmids / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction; D013696:Temperature; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009841:Oligonucleotides; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C071731:SIN3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases; D021984:Cyclophilin A; C000606845:ESS1 protein, S cerevisiae; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase