Cell divisions in the drosophila embryonic mesoderm are repressed via posttranscriptional regulation of string/cdc25 by HOW.
BACKGROUND
Cell-cycle progression is tightly regulated during embryonic development. In the Drosophila early embryo, the levels of String/Cdc25 define the precise timing and sites of cell divisions. However, cell-cycle progression is arrested in the mesoderm of gastrulating embryos despite a positive transcriptional string/cdc25 activation provided by the mesoderm-specific action of Twist. Whereas String/Cdc25 is negatively regulated by Tribbles in the mesoderm at these embryonic stages, the factor(s) controlling string/cdc25 mRNA levels has yet to be elucidated.


RESULTS
Here, we show that the repressor isoform of the Drosophila RNA binding protein Held Out Wing [HOW(L)] is required to inhibit mesodermal cell division during gastrulation. Embryos mutant for how exhibited an excess of cell divisions, leading to delayed mesoderm invagination. The levels of the mitotic activator string/cdc25 mRNA in these embryos were significantly elevated. Protein-RNA precipitation experiments show that HOW(L) binds string/cdc25 mRNA. Overexpression of HOW(L) in Schneider cells reduces specifically the steady-state mRNA levels of a gfp reporter fused to string/cdc25 untranslated region (3'UTR).


CONCLUSIONS
Our results suggest that in wild-type embryos, string/cdc25 mRNA levels are downregulated by the repressor isoform HOW(L), which binds directly to string/cdc25 mRNA and regulates its degradation. Thus, we are proposing a novel posttranscriptional mechanism controlling cell-cycle progression in the Drosophila embryo.
Nabel-Rosen
Helit
H
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Toledano-Katchalski
Hila
H
Volohonsky
Gloria
G
Volk
Talila
T
D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000502:physiology*; D002478:Cells, Cultured; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D005775:Gastrula / Q000378:metabolism; D007150:Immunohistochemistry; D008648:Mesoderm / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D034622:RNA Interference / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C106296:how protein, Drosophila; D017027:Protein Tyrosine Phosphatases; C059217:stg protein, Drosophila