Mechanisms of maternal mRNA regulation: implications for mammalian early embryonic development

Abstract

Mammalian oocytes accumulate a large pool of mRNA molecules that orchestrate subsequent embryonic development. The transcriptional machinery is silent during oocyte meiotic maturation and early embryogenesis, and thereby the early decisive events in embryo development prior to initiation of transcription from the embryonic genome are directed by the translation of pre-existing maternal mRNAs. Oocytes display remarkable post-transcriptional regulatory mechanisms that control mRNA stability and translation. The regulatory mechanisms are generally negative, and target mRNAs are either subjected to degradation or repressed from undergoing translation until specifically activated. Such negative regulatory mechanisms generally are mediated by transcript deadenylation, interaction of transcripts with RNA-binding proteins in a nonspecific or sequence-specific fashion, and/or potentially via actions of microRNA and repeat- associated small interfering RNA, which degrade maternal RNA transcripts. In contrast, translational activation is initiated via cytoplasmic polyadenylation of maternal transcripts facilitated via the binding of embryo-specific poly(A)-binding proteins (ePABs). In certain instances, translational regulation (positive or negative) is dictated by the balance of positive and negative trans-acting factors that compete for specific sequence motifs present in maternal transcripts. Coordinate post-transcriptional regulation of the oocyte mRNA pool is critical for normal progression of early embryonic development.