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Characterization of the Drosophila Rae1 protein as a G1 phase regulator of the cell cycle
1EMBL, Meyerhofstrasse 1, D-69117 Heidelberg, Germany. Delphine.Sitterlin@genetique.uvsq.fr
Abstract:
Messengers RNA (mRNA) are thought to be export from the nucleus as ribonucleoprotein complexes (mRNP), whose exact protein composition remains not completely determined. The Gle2/RAE1 protein, a highly conserved member of the WD40 repeat protein family, was first shown to be involved in mRNA export. More recently, a role in the cell cycle was also suggested. To get new insights into the functions of the metazoan protein, the Drosophila melanogaster rae1 (dmrae1) cDNA was first cloned, then the corresponding protein characterized and its function investigated by RNA interference. This paper shows that dmRae1 mainly localises to the nuclear membrane like its homologue in Saccharomyces cerevisiae. However, unlike its homologue and despite this particular sub-cellular distribution, its depletion does not impair the export of polyA+ RNAs. Interestingly, the presence of dmRae1 is important for normal proliferation and, more importantly, for the progression through the G1 phase of the cell cycle. Given that dmRae1 is closely related to the human form, results suggest that the human homologue, hsRAE1, may also play a similar role during the cell cycle.
Insights
Messenger RNA (mRNA) export involves ribonucleoprotein complexes (mRNP). The study investigated the role of the Gle2/RAE1 protein in Drosophila, finding it crucial for cell cycle progression, not mRNA export.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Messenger RNA (mRNA) is exported from the nucleus as ribonucleoprotein complexes (mRNP).
- The Gle2/RAE1 protein, a conserved WD40 repeat protein, is implicated in mRNA export and cell cycle regulation.
- Understanding metazoan RAE1 function requires further investigation.
Purpose of the Study:
- To clone and characterize the Drosophila melanogaster rae1 (dmrae1) cDNA.
- To investigate the function of dmRae1 in mRNA export and cell cycle progression.
- To explore potential roles of the human homologue, hsRAE1.
Main Methods:
- Cloning of dmrae1 cDNA.
- Characterization of the dmRae1 protein.
- RNA interference (RNAi) for functional analysis.
- Sub-cellular localization studies.
- Analysis of polyA+ RNA export and cell proliferation.
Main Results:
- dmRae1 localizes to the nuclear membrane, similar to its yeast homologue.
- Depletion of dmRae1 did not affect polyA+ RNA export.
- dmRae1 is essential for normal cell proliferation and G1 phase progression.
- dmRae1 shares functional similarities with its human homologue.
Conclusions:
- dmRae1 plays a critical role in cell cycle progression, specifically in the G1 phase.
- Contrary to expectations, dmRae1 is not essential for mRNA export in Drosophila.
- Results suggest a conserved role for RAE1 proteins in cell cycle regulation across species.
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