Post-Transcriptional Regulation of Maternal mRNA Shapes Early C. Elegans Embryogenesis

Much of early embryogenesis is controlled through complex networks comprised of maternally provided factors. Oocytes are packed with protein and RNA that are ready to spring into action after fertilization to guide early embryonic development. The regulation of maternally provided factors is therefore critical and is a fundamental goal of developmental biology. During my studies, I investigated how two maternally provided mRNAs, zif-1 and mom-2, are regulated post-transcriptionally through their 3’ untranslated region (3’ UTR) to ensure proper spatio-temporal protein expression. I discovered that seven RNA binding proteins bind directly to the zif-1 3’ UTR in a combinatorial fashion thereby ensuring that zif-1 is only translated in somatic blastomeres, beginning at the four cell stage embryo. Interestingly a similar set of RNA binding proteins (nine total) regulate the spatio-temporal expression of mom-2 in a similar fashion despite the fact that mom-2 has a reciprocal expression pattern when compared to zif-1. My studies on zif-1 and mom-2 regulation indicate that a “code” is embedded within the 3’ UTR of mRNAs to mediate translational regulation. The precise combination of RNA binding proteins present in a particular cell at a particular time, each with the intrinsic capability of binding to regulatory sequences contained in this “code”, determines when and where mRNAs get translated. I also investigated mechanisms by which maternal mRNAs get degraded. Zygotic transcription activation is often linked to maternal mRNA degradation, which I showed to be the case in C. elegans embryos. Specifically, I discovered a gene termed vet-5 that is first transcribed in the somatic blastomeres of the four-cell embryo and is sufficient to degrade at least several maternal mRNAs when provided exogenously as dsRNA. vet-5 maps to a highly repetitive locus and has been shown to be a target of siRNA production. Consistent with vet-5 derived siRNA production I found that the siRNA pathway is, at least partly, required for the degradation of maternal mRNAs and that removing components of the siRNA pathway affects vet-5 expression. Therefore, I hypothesize that siRNAs could be produced from the vet-5 locus that target maternally provided mRNAs for degradation.