Kappei Tsukahara

Isolation of a Mammalian Homologue of a Fission Yeast Differentiation Regulator

ABSTRACT In the fission yeast Schizosaccharomyces pombe thenrd1 + 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. pombetemperature-sensitive pat1 mutant that commits lethal haploid meiosis at the restrictive temperature, we have clonedROD1, a functional homologue ofnrd1 +, from rat and human cDNA libraries. Likenrd1 +, 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 tonrd1 +, being able to repress Ste11-regulated genes and to inhibit conjugation upon overexpression. ROD1is 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.

An RNA Binding Protein Negatively Controlling Differentiation in Fission Yeast

ABSTRACT The fission yeast Schizosaccharomyces pombe starts sexual development when starved for nutrients and simultaneously activated by mating pheromones. We have identified a new gene regulating the onset of this process. This gene, callednrd1+, encodes a typical RNA binding protein that preferentially binds poly(U). Deletion ofnrd1 + causes cells to initiate sexual development without nutrient starvation. We have found that the biological role of nrd1 + is to block the onset of sexual development by repressing the Ste11-regulated genes essential for conjugation and meiosis until cells reach a critical level of starvation.