Abstract
Zfrp8/PDCD2 is a highly conserved protein essential for stem cell maintenance in both flies and mammals. It is also required in fast proliferating cells such as cancer cells. Our previous studies suggested that Zfrp8 functions in the formation of mRNP (mRNA ribonucleoprotein) complexes and also controls RNA of select Transposable Elements (TEs). Here we show that in Zfrp8/PDCD2 knock down (KD) ovaries, specific mRNAs and TE transcripts show increased nuclear accumulation. We also show that Zfrp8/PDCD2 interacts with the (40S) small ribosomal subunit through direct interaction with RpS2 (uS5). By studying the distribution of endogenous and transgenic fluorescently tagged ribosomal proteins we demonstrate that Zfrp8/PDCD2 regulates the cytoplasmic levels of components of the small (40S) ribosomal subunit, but does not control nuclear/nucleolar localization of ribosomal proteins. Our results suggest that Zfrp8/PDCD2 functions at late stages of ribosome assembly and may regulate the binding of specific mRNA-RNPs to the small ribosomal subunit ultimately controlling their cytoplasmic localization and translation.
Highlights
PDCD2 is an evolutionarily conserved eukaryotic protein, that is required in stem- and embryonic cells of many different organisms and facilitates cancer cell growth [1,2,3,4,5]
Upon close inspection of these ovaries we detected abnormalities in germline stem cells (GSCs) divisions, abnormal spectrosomes, and a delay in egg chamber growth (S1C– S1H Fig). This phenotype is similar to the phenotype observed when Zfrp8 is depleted in the germline either by induction of Zfrp8 clones or germline specific knock down (KD) [8]
We have found that Zfrp8/PDCD2 interacts with RpS2 in a number of assays, including the yeast two-hybrid, consistent with direct interaction between the two proteins
Summary
PDCD2 is an evolutionarily conserved eukaryotic protein, that is required in stem- and embryonic cells of many different organisms and facilitates cancer cell growth [1,2,3,4,5]. It is essential in mouse embryonic stem cells and PDCD2 knock out embryos die prior to implantation [2, 4]. Zfrp8/PDCD2 is essential for the maintenance of hematopoietic stem cells in Drosophila [7] and in follicle and germline stem cells (GSCs) in the ovary [8]. Lack of Zfrp causes an arrest of stem cell division and ultimate
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