The DNA/RNA-binding protein MSY2 marks specific transcripts for cytoplasmic storage in mouse male germ cells

Abstract

During spermatogenesis, male germ cells temporally synthesize many proteins as they differentiate through meiosis and become spermatozoa. The germ cell Y-box protein, MSY2, constituting Ϸ0.7% of total protein in male germ cells, binds to a consensus promoter element, and shows a general lack of RNA-binding specificity. Combining immunoprecipitation and suppressive subtractive hybridization, we identified populations of germ cell mRNAs that are not bound or bound by MSY2. The former population is enriched in cell growth and ubiquitously expressed mRNAs, whereas the latter population is enriched for stored or translationally delayed, male gamete-specific transcripts. Chromatin precipitation assays reveal that most of the MSY2 target mRNAs are transcribed from genes containing the Y-box DNA-binding motif in their promoters. In transgenic mice, mRNAs encoding exogenous GFP are directed or not directed into the MSY2-bound fraction by promoters containing or lacking the Y-box motif, respectively. We propose that MSY2 marks specific mRNAs in the nucleus for cytoplasmic storage, thereby linking transcription and mRNA storage͞translational delay in meiotic and postmeiotic male germ cells of the mouse.mRNA storage ͉ spermatogenesis ͉ transcription and translation linkage ͉ Y-box protein

Expression profiling reveals meiotic male germ cell mRNAs that are translationally up- and down-regulated

“…CPEB binds to the cytoplasmic polyadenylation element, modulating translational repression during oocyte maturation, and is involved in mRNA localization in neuronal synapses (47). In the testis, a number of proteins, including TSN, bind to Prm2 mRNAs during its translational repression (1,(48)(49)(50), suggesting a variety of RNA-protein complexes can be formed with germ cell mRNAs. In addition to transporting postmeiotically expressed mRNAs (12), the RNAbinding protein TSN binds to meiotic noncoding RNAs and meiotic mRNAs, such as Dbil5, in the nuclei of spermatocytes (51).…”

GDNF Signaling Regulates YBX1/mRNA Interactions in Mouse Spermatogonia.

“…Because YBX1 is regulating the translation of genes that are known to be important for spermatogenesis (such as DAZL and PLZF), we predict that this protein is critical to normal SSC function. While we cannot discount the possibility that YBX1 is redundant in function, there is significance that another Y-box protein, MSY2, is only expressed in later spermatogenic cells and is necessary for spermatogenesis because of its function in translational regulation [210,223,224]. It occurs to us that YBX1 and MSY2 may be performing similar functions in different cells.…”

Transcription and post-transcriptional regulation of spermatogenesis

“…To begin to understand the molecular role of MSY2 in spermatogenesis, Yang et al (2005a) identified mRNAs specifically bound by MSY2 in male germ cells. They found that the majority of the MSY2-bound mRNAs had a Y-box DNA sequence motif in the promoter region of their respective genes.…”