Jayesh Sundarum, Lee Lab
Decoding principles underlying maternal mRNA degradation in zebrafish embryos
Pluripotency refers to the property of embryonic stem cells that allows them to give rise to all other cell types in an organism. Pluripotency induction during early embryonic development requires transcriptome reprogramming - i.e., transcription of new mRNAs and degradation of unwanted mRNAs. Across animals, including in our model system zebrafish, the early embryo is transcriptionally silent and relies on maternally contributed mRNAs for its cellular functions. Later, when the embryonic genome has been activated, these maternal mRNAs are subsequently degraded through regulated clearance. The mechanisms underlying maternal mRNA clearance in vertebrate embryos are not well understood. In zebrafish, maternal clearance largely depends on de-novo transcription. Thus far, the only characterized transcription-dependent mechanism relies on the de-novo transcribed microRNA miR-430. However, miR-430 regulates only 11% of cleared maternal mRNAs, indicating that additional unknown mechanisms regulate maternal clearance in zebrafish. To discover novel clearance mechanisms, we first identified distinct groups of maternal mRNAs with correlated clearance patterns across RNA-seq datasets from embryos with various defects in early development. Next, to identify candidate factors regulating degradation of mRNAs in those groups, I searched for de novo transcribed genes whose expression patterns were highly correlated with the clearance patterns of the maternal mRNA, which revealed the RNA binding proteins Mex3a/b among the best candidates. Mex3 orthologs have previously been shown to regulate translational repression and mRNA degradation in other organisms, suggesting that Mex3a/b may play similar roles in zebrafish embryos, which I will investigate in the future. Additionally, some of the maternal mRNA groups were enriched in putative destabilizing sequence motifs, suggesting other shared mechanisms regulate the clearance of these mRNAs. Finally, some of the maternal mRNA groups lacked any shared sequence patterns, suggesting the existence of novel mRNA regulatory mechanisms in the early embryo. Overall, our findings will further elucidate the mechanisms underlying transcriptome reprogramming and pluripotency induction across vertebrates.
Friday, June 5, 2020
12PM