Translational regulation:miRNA processing and RISC function during Xenopus oogenesis & embryogenesis
My research uses a combination of molecular, cellular and biochemical approaches to address the developmental regulation of miRNA processing and RISC function during Xenopus oogenesis and embryogenesis.
MicroRNAs (miRNAs) are small, non-coding RNAs that post-transcriptionally control gene expression by directing either the degradation or translational repression of target mRNAs. miRNAs potentially regulate as many as one-third of all protein-coding genes in vertebrates and have essential roles in controlling diverse aspects of cellular function in numerous physiological contexts. They are particularly important in silencing cell cycle genes that direct cellular proliferation. miRNA biogenesis is a complex process involving distinct multimeric complexes that catalyze sequential RNA processing events. Primary miRNA transcripts are initially processed in the nucleus by the microprocessor complex comprised of Drosha and DGCR8. The resultant pre-miRNAs are exported into the cytoplasm and converted to mature miRNAs by Dicer and bind to the Argonaute (Ago) family of proteins to form the RNA-induced-silencing complex (RISC).
The maternal mRNAs encoding Ago2, DGCR8, Dicer and Drosha are translationally repressed in immature oocytes. Although the processing proteins are present in fully-grown oocytes, miRNA processing is not activated until progesterone-induced meiotic maturation is completed. We are also investigating how the RISC participates in the "egg-to embryo switch" that occurs at the midblastula transition when maternal mRNAs are degraded concomitant with the activation of zygotic transcription. Our goal is to identify the miRNAs and their corresponding mRNA targets that are recruited into the RISC in order to direct the maternal to zygotic transition that enables cellular specialization to ensue after the embryonic cell cycles are attenuated.
University of Virginia
Web Page: http://minerva.acc.virginia.edu/~biology/Fac/Wormington.html