IMP dehydrogenase is recruited to the transcription complex through serine 2 phosphorylation of RNA polymerase II.
IMP dehydrogenase (IMPDH) catalyzes the rate-limiting step in the de novo synthesis of guanine, namely the oxidation of IMP to XMP with a concomitant reduction of NAD+. In Saccharomyces cerevisiae, a family of four closely-related genes, IMD1, IMD2 (also known as PUR5), IMD3, and IMD4, encodes the putative IMPDH. Although IMPDH synthesizes guanine in the cytoplasm, it has also been found in the nucleus, where it associates with nucleic acids in human cells. Here, we further show that IMPDH is recruited to actively transcribed region of genes. A synthetic lethal screen using a deletion strain of Ctk1 kinase, a yeast homolog of mammalian Cdk9/P-TEFb that phosphorylates serine 2 within the RNA polymerase II (RNApII) C-terminal domain (CTD), identified that Imd2 genetically interacts with Ctk1. Consistent with this association, IMPDHs were recruited to elongating RNApII only when serine 2 of the CTD was phosphorylated by Ctk1. Loss of Imd2 had little effect on the association of most elongation factors with RNApII. However, in cells lacking Imd2 or all the essential IMPDHs in the presence of minimal guanine, a defect in the association of Ctk1 with the promoter region was seen. Taken together, our results show that IMPDH is recruited to transcription complex through serine 2 phosphorylation of RNApII CTD and suggest that it may play a role in initiating transcriptional regulation.
Park
Jae-Hyun
JH
Department of Biochemistry and Molecular Biology, College of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
Ahn
Seong Hoon
SH
D015966:Gene Expression Regulation, Fungal; D007168:IMP Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D029701:Saccharomyces cerevisiae Proteins; D012694:Serine; D007168:IMP Dehydrogenase; D012319:RNA Polymerase II; C511736:RPB1 protein, S cerevisiae