Absence of MSY2 in Mouse Oocytes Perturbs Oocyte Growth and Maturation, RNA Stability, and the Transcriptome

Abstract

Messenger RNA is remarkably stable during oocyte growth, thus enabling mRNAs to accumulate during the growth phase and thereby provide mRNAs that support early embryonic development. MSY2, a germ cell-specific RNA-binding protein, is implicated in regulating mRNA stability. MSY2 is essential for development because female Msy2(-/-) mice are infertile. We describe here the characterization of Msy2(-/-) oocytes. Mutant oocytes grow more slowly during the first wave of folliculogenesis, and maturation to and arrest at metaphase II is severely compromised because of aberrant spindle formation and chromosome congression. Consistent with MSY2 conferring mRNA stability is that the amount of poly(A)-containing RNA is reduced by ~25% in mutant oocytes. Stability of an exogenous mRNA injected into mutant oocytes is lower than when compared to their wild-type counterparts, and moreover, expression of wild-type MSY2 in mutant oocytes increases mRNA stability, whereas injection of a mutant form of MSY2 not capable of binding RNA does not. Transcription quiescence that normally occurs during the course of oocyte growth is not observed in mutant oocytes, and the transcriptome of mutant oocytes is markedly perturbed. These results, and those of previous studies, strongly implicate a central role of MSY2 in regulating mRNA stability.

Epigenetic inheritance through the female germ-line: The known, the unknown, and the possible

“…Although the initiation of oocyte growth is accompanied by widespread changes in the pattern of gene transcription, there is little evidence to date of substantial qualitative changes in the transcriptome during the period of growth [24,25]. In contrast, there is extensive post-transcriptional control of gene expression [26,27]. Many messenger RNAs are not translated but are instead rapidly deadenylated at the 3 -poly(A) tail following export from the nucleus and stored, possibly in large ribonucloprotein complexes located near the cortex of the oocyte [28,29].…”

Losing Mom’s Message: Requirement for DCP1A and DCP2 in the Degradation of Maternal Transcripts During Oocyte Maturation1

“…Reducing MSY2 protein using a transgenic RNA interference (RNAi) approach leads to a decrease in protein synthesis and in the total amount of RNA; in turn, this leads to abnormal meiotic spindle formation and low incidence of egg activation after fertilization [12]. Furthermore, Msy2 À/À oocytes have a reduced growth rate compared with wild-type oocytes; these knockout oocytes fail to become transcriptionally quiescent when fully grown, display a decrease in mRNA stability, and do not mature properly [13]. A progressive loss of oocytes and follicles as well as disrupted ovulation also occur in Msy2 À/À mice, with the result that these mice are infertile [14].…”

Follicular environment and oocyte maturation: roles of local peptides and steroids

“…Kit ligand did not alter mRNA levels of NPR2, but decreased mRNA abundance of NPPC in bovine cumulus cells. In addition, KL increased expression of Y-box binding protein 2 (YBX2) in the oocyte, a protein that regulates RNA stability and protein synthesis and is required for normal spindle formation (Medvedev et al, 2011). Finally, we assessed whether the oocyte regulates KL expression in cumulus cells using the oocytectomy model, and observed mRNA levels around 5 times more abundant in oocytectomized compared with intact COCs at the end of IVM.…”