oocyte-to-embryo transition, RNA degradation, RNAi, miRNA, retrotransposon
Retrotransposons & evolving gene control during oocyte-to-embryo transition
Our broad research interests (Fig. 1) converge at understanding evolving molecular mechanisms governing control of gene expression during mammalian oocyte-to-embryo transition (OET, Fig. 2). It is an intriguing highly orchestrated process resulting in cell fate reprogramming, which is one of the key themes of stem cell biology (Fig. 3). At the beginning of OET, there is a highly specialized cell – the oocyte, which resumes and completes meiosis while being released from the ovary. Subsequent fertilization yields a zygote, which activates its genome-encoded developmental program. A successful zygotic genome activation (ZGA) is an essential event in the life of every sexually reproducing organism. Importantly, ZGA is closely associated with acquisition of pluripotency, i.e. the ability of a cell to differentiate into any body cell type. Our lab explores a complex of inter-related aspects of control of gene expression during OET and their changes during evolution. Our current research can be divided into two broad areas described below.
Evolution of maternal transcriptomes and their regulations
Genomes evolve. Consequently, genes and their expression during OET evolve as well (Fig. 4). We study, which evolutionary adaptations in mouse oocytes are mouse-specific and which are ancestral, i.e. representing common principles of oocyte biology. One of the factors contributing to genome evolution are mobile elements. We are particularly interested in impact of a class of long terminal repeat (LTR) retrotransposons, which resemble mobile gene-remodeling platforms that supply promoters and first exons. LTRs of these mobile elements affect in a stage-specific manner OET by controlling transcription, altering protein-coding sequences, and supporting evolution of new genes. Accordingly, we study new biological functions evolved from stochastic genome remodeling by LTRs.
Role of small RNAs during OET
Small RNAs guiding repressive ribonucleoprotein complexes represent a unique layer of control of gene expression and retrotransposon activity. Our ERC-funded research focuses on the role of small RNAs (microRNAs, short interfering RNAs (siRNAs) and PIWI-associated RNAs (piRNAs)) in the mammalian female germline. Our primary research model are mouse oocytes, which offer an opportunity to study a unique co-existence of all three classes of small RNAs. Remarkably, only siRNAs acting in the RNA interference (RNAi) pathway are essential for OET in mice. We explore the molecular foundation of highly active RNAi in mouse oocytes: a unique maternal isoform of Dicer, which is responsible for highly efficient siRNA production and an evolving set of long non-coding RNAs carrying antisense pseudogene sequences, which give rise to siRNAs, which in turn suppress complementary mRNA. Research questions we wish to answer include: Which molecular mechanisms are controlled by RNAi in mouse oocytes? How small RNA pathways operate in oocytes of other mammals? What are the consequences of ectopically enhanced RNAi in somatic cells?
Last change: October 23, 2019