Mingyi Xie, Ph.D.
Research: Gene expression regulation by non-coding RNAs; microRNA biogenesis
Ph.D from Arizona State University, 2010
From 2005 to 2010, Dr. Xie’s Ph.D. work focused on investigating the structure and function of vertebrate telomerase, under the guidance of Dr. Julian Chen at Arizona State University. In 2010, he joined the laboratory of Dr. Joan Steitz at Yale University to study non-canonical microRNA (miRNA) biogenesis in Herpesviruses and their mammalian hosts. Dr. Xie joined the faculty at the University of Florida in September, 2016.
MiRNAs are ~22 nucleotide (nt) ubiquitous gene regulators that modulate diverse cellular pathways including differentiation, proliferation and apoptosis, all critical to human development and diseases. Canonical miRNAs are produced from long primary (pri-) miRNA transcripts that are cleaved by the nuclear Microprocessor complex, with the resulting precursor (pre-) miRNA hairpins exported by Exportin-5 and processed by cytoplasmic Dicer to yield mature miRNAs (Fig. 1, middle panel). At Yale, Dr. Xie documented two surprising miRNA biogenesis pathways:
- Herpesvirus saimiri (HVS)-miRNAs are processed by the host Integrator complex, a 14-subunit complex best known for executing the 3′-end cleavage of cellular small nuclear RNAs (snRNAs), therefore bypassing the canonical Microprocessor cleavage. (Fig. 1, top panel)
- Mammalian m7G-capped precursor miRNAs are generated from RNA polymerase (Pol) II transcription initiation sites. Whereas the nuclear-cytoplasmic export of capped pre-miRNAs is mediated by Exportin-1. (Fig.1 bottom panel)
These pathways surprisingly incorporate fundamental cellular machineries involved in processing other classes of RNAs, expanding our appreciation of their impact on small RNA populations and oncogenesis. Our group’s immediate research goal is to further delineate the unique modes of miRNA production, including Integrator-mediated RNA metabolism, and understand the functions of these special miRNAs in herpesviruses and their hosts. Such research will allow the design of therapies for related oncogenic herpesviruses and cancers.