Isolation of a mammalian homologue of a fission yeast differentiation regulator.
In the fission yeast Schizosaccharomyces pombe the nrd1(+) gene encoding an RNA binding protein negatively regulates the onset of differentiation. Its biological role is to block differentiation by repressing a subset of the Ste11-regulated genes essential for conjugation and meiosis until the cells reach a critical level of nutrient starvation. By using the phenotypic suppression of the S. pombe temperature-sensitive pat1 mutant that commits lethal haploid meiosis at the restrictive temperature, we have cloned ROD1, a functional homologue of nrd1(+), from rat and human cDNA libraries. Like nrd1(+), ROD1 encodes a protein with four repeats of typical RNA binding domains, though its amino acid homology to Nrd1 is limited. When expressed in the fission yeast, ROD1 behaves in a way that is functionally similar to nrd1(+), being able to repress Ste11-regulated genes and to inhibit conjugation upon overexpression. ROD1 is predominantly expressed in hematopoietic cells or organs of adult and embryonic rat. Like nrd1(+) for fission yeast differentiation, overexpressed ROD1 effectively blocks both 12-O-tetradecanoyl phorbol-13-acetate-induced megakaryocytic and sodium butyrate-induced erythroid differentiation of the K562 human leukemia cells without affecting their proliferative ability. These results suggest a role for ROD1 in differentiation control in mammalian cells. We discuss the possibility that a differentiation control system found in the fission yeast might well be conserved in more complex organisms, including mammals.
Yamamoto
H
H
Department of Biochemistry and Molecular Biology, Graduate School of Medicine, The University of Tokyo, Bunkyo-Ku, Tokyo 113-0033, Japan.
Tsukahara
K
K
Kanaoka
Y
Y
Jinno
S
S
Okayama
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002087:Butyrates / Q000494:pharmacology; D002454:Cell Differentiation / Q000235:genetics*; D003001:Cloning, Molecular; D005434:Flow Cytometry; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics; D011068:Poly G / Q000378:metabolism; D011072:Poly U / Q000378:metabolism; D038941:Polypyrimidine Tract-Binding Protein; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D051381:Rats; D012261:Ribonucleoproteins / Q000737:chemistry; D012568:Schizosaccharomyces / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured
D002087:Butyrates; D005656:Fungal Proteins; D009363:Neoplasm Proteins; C118823:PTBP3 protein, human; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C491210:nrd1 protein, S pombe; D038941:Polypyrimidine Tract-Binding Protein; C071596:ste11 protein, S pombe; D011068:Poly G; D011072:Poly U; D013755:Tetradecanoylphorbol Acetate