W. Michael Wormington
- PhD, University of Kansas
- Associate Professor, Biology
- Phone: 434-982-5803
- Email: firstname.lastname@example.org
- Website: http://www.virginia.edu/biology/faculty/wormington.htm
Regulation of miRNA Processing and Function During 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).
My research uses a combination of molecular , cellular and biochemical approaches to address the develop-mental regulation of miRNA processing and RISC function during Xenopus oogenesis and embryogenesis. 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.
- Zero tolerance for nonsense: nonsense-mediated mRNA decay uses multiple degradation pathways. Molecular cell. 2003;12(3): 536-8. PMID: 14527400
- Schneider R, Agol V, Andino R, Bayard F, Cavener D, Chappell S, Chen J, Darlix J, Dasgupta A, Donzé O, Duncan R, Elroy-Stein O, Farabaugh P, Filipowicz W, Gale M, Gehrke L, Goldman E, Groner Y, Harford J, Hatzglou M, He B, Hellen C, Hentze M, Hershey J, Hershey P, Hohn T, Holcik M, Hunter C, Igarashi K, Jackson R, Jagus R, Jefferson L, Joshi B, Kaempfer R, Katze M, Kaufman R, Kiledjian M, Kimball S, Kimchi A, Kirkegaard K, Koromilas A, Krug R, Kruys V, Lamphear B, Lemon S, Lloyd R, Maquat L, Martinez-Salas E, Mathews M, Mauro V, Miyamoto S, Mohr I, Morris D, Moss E, Nakashima N, Palmenberg A, Parkin N, Pe'ery T, Pelletier J, Peltz S, Pestova T, Pilipenko E, Prats A, Racaniello V, Read G, Rhoads R, Richter J, Rivera-Pomar R, Rouault T, Sachs A, Sarnow P, Scheper G, Schiff L, Schoenberg D, Semler B, Siddiqui A, Skern T, Sonenberg N, Sossin W, Standart N, Tahara S, Thomas A, Toulmé J, Wilusz J, Wimmer E, Witherell G, Wormington M. New ways of initiating translation in eukaryotes. Molecular and cellular biology. 2001;21(23): 8238-46. PMID: 11710333 | PMCID: PMC99989
- Varnum S, Hurney C, Wormington W. Maturation-specific deadenylation in Xenopus oocytes requires nuclear and cytoplasmic factors. Developmental biology. 1992;153(2): 283-90. PMID: 1397685
- Keiper B, Wormington W. Nucleotide sequence and 40 S subunit assembly of Xenopus laevis ribosomal protein S22. The Journal of biological chemistry. 1990;265(32): 19397-400. PMID: 2246230
- Varnum S, Wormington W. Deadenylation of maternal mRNAs during Xenopus oocyte maturation does not require specific cis-sequences: a default mechanism for translational control. Genes & development. 1990;4(12): 2278-86. PMID: 1980656
- Developmental expression and 5S rRNA-binding activity of Xenopus laevis ribosomal protein L5. Molecular and cellular biology. 1989;9(12): 5281-8. PMID: 2586520 | PMCID: PMC363692
- Krieg P, Varnum S, Wormington W, Melton D. The mRNA encoding elongation factor 1-alpha (EF-1 alpha) is a major transcript at the midblastula transition in Xenopus. Developmental biology. 1989;133(1): 93-100. PMID: 2707491