Role of CK2-dependent phosphorylation of Ifh1 and Crf1 in transcriptional regulation of ribosomal protein genes in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, Fhl1 is involved in the regulation of ribosomal protein (RP) genes through interaction with either its coactivator Ifh1 or corepressor Crf1, depending on nutrient conditions. Interaction of Fhl1 with Ifh1 or Crf1 is achieved through a forkhead-associated (FHA) domain of Fhl1, which binds to forkhead-binding (FHB) domains of Ifh1 and Crf1. Here, we demonstrate that CK2-dependent phosphorylation of T681 and T348 residues, located in the FHB domains of Ifh1 and Crf1, respectively, provides binding sites for the FHA domain of Fhl1. Cells expressing Ifh1(T681A) mutant showed reduced association of Ifh1 at the RP gene promoters and decreased levels of RP gene transcripts, thereby reducing the growth rate. On the other hand, cells expressing Crf1(T348A) showed a defect in repressing RP gene transcription upon inhibition of target of rapamycin complex 1 (TORC1) by rapamycin treatment. Taken together, these findings suggest the mechanisms by which CK2-dependent recruitment of Ifh1 and Crf1 at the RP gene promoters governs the transcription of RP genes.