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 sup pression of the S. pombe temperature-sensitive pat1 mutant that commits let hal haploid meiosis at the restrictive temperature, we have cloned ROD1, a functional homologue of nrd1(+), from rat and human cDNA libraries. Like nr d1(+), ROD1 encodes a protein with four repeats of typical RNA binding doma ins, though its amino acid homology to Nrd1 is limited. When expressed in t he fission yeast, ROD1 behaves in a way that is functionally similar to nrd 1(+), being able to repress Ste11-regulated genes and to inhibit conjugatio n upon overexpression. ROD1 is predominantly expressed in hematopoietic cel ls or organs of adult and embryonic rat. Like nrd1(+) for fission yeast dif ferentiation, overexpressed ROD1 effectively blocks both 12-O-tetradecanoyl phorbol-13-acetate-induced megakaryocytic and sodium butyrate-induced eryt hroid differentiation of the K562 human leukemia cells without affecting th eir proliferative ability. These results suggest a role for ROD1 in differe ntiation control in mammalian cells. We discuss the possibility that a diff erentiation control system found in the fission yeast might well be conserv ed in more complex organisms, including mammals.