Ph.D. Duke University 2004
MicroRNA-mediated regulation in mammalian skin development, stem cells and cancer
Mammalian skin and its appendages function as the outermost barrier of the body to protect inner organs from environmental hazards and keep essential fluid within. During embryonic development, a single layer of multipotent epidermal stem cells gives rise to the epidermis, hair follicle and sebaceous gland, a process orchestrated by an array of regulatory pathways (see the figure).
In adult, homeostasis of each of three skin lineages is maintained through self-renewal and differentiation of distinct skin stem/progenitor cells. Through extensive investigation, much has been learned about the regulatory networks that control skin morphogenesis during embryonic development and self-renewal and differentiation of adult skin stem/progenitor cells. Recently, however, a novel layer of regulation mediated by miRNAs is implicated in mammalian development and diseases.
MiRNAs are a family of non-coding small RNAs (~19-24nt) expressed in a wide range of animals and plants. This newly discovered RNA species counts for 1-3% genes in mammalian genome. It is estimated that more than one third of protein-encoding mRNAs are regulated by miRNAs. In turn, miRNA-mediated regulation is believed to have a widespread impact on both protein output of transcriptome and evolution of gene regulatory networks. MiRNAs' potentials in globally regulating gene expression and developmental transitions during mammalian skin development have dramatically escalated interests in these novel regulators.
We are interested in the elucidation of microRNA-mediated regulatory networks in mammalian skin development, stem cells and cancer. Specifically, we are developing research programs in the following areas: 1) comprehensive profiling and analysis microRNA's expression pattern in different skin lineages and skin cancer; 2) investigation of individual microRNA's functions with combinatorial approaches in mouse genetics, cell biology, molecular biology and biochemistry; 3) elucidating the molecular mechanisms of microRNA's functions by systematically identifying their physiological targets; 4) exploring potential roles of other regulatory RNAs in mammalian skin
High-efficiency RNA cloning enables accurate quantification of miRNA expression by deep sequencing
Zhang Z, Lee JE, Riemondy K, Anderson EM, and Yi R. (2013). Genome Biology 2013, 14:R109.
MicroRNA-205 controls neonatal expansion of skin stem cells by modulating the PI(3)K pathway
Wang D, Zhang Z, O'Loughlin E, Wang L, Fan X, Lai EC and Yi R (2013). Nature Cell Biology. 2013. Epub 2013 Aug 25.
Rapid and widespread suppression of self-renewal by microRNA-203 during epidermal differentiations
Sarah J. Jackson, Zhaojie Zhang, Dejiang Feng, Meaghan Flagg, Evan O'Loughlin, Dongmei Wang, Nicole Stokes, Elaine Fuchs, and Rui Yi (2013)
Development 2013 140:1882-1891; doi:10.1242/dev.089649
Genome-wide maps of polyadenylation reveal dynamic mRNA 3'-end formation in mammalian cell lineages
Wang L, Dowell RD, Yi R. (2013)
RNA. 2013 Jan 16. 23325109
Quantitative functions of Argonaute proteins in mammalian development.
Wang D, Zhang Z, O'Loughlin E, Lee T, Houel S, O'Carroll D, Tarakhovsky A, Ahn NG, Yi R. Genes Dev. 2012 Apr 1;26(7):693-704.
A miR image of stem cells and their lineages.
Yi R, Fuchs E. Curr Top Dev Biol. 2012;99:175-99. Review.
MicroRNAs and their roles in mammalian stem cells.
Yi R, Fuchs E. J Cell Sci. 2011 Jun 1;124(Pt 11):1775-83. Review.
MicroRNA-mediated control in the skin.
Yi R, Fuchs E. Cell Death Differ. 2010 Feb;17(2):229-35. Epub 2009 Jul 17. Review.
DGCR8-dependent microRNA biogenesis is essential for skin development.
Yi R, Pasolli HA, Landthaler M, Hafner M, Ojo T, Sheridan R, Sander C, O'Carroll D, Stoffel M, Tuschl T, Fuchs E. Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):498-502. Epub 2008 Dec 29.
A skin microRNA promotes differentiation by repressing 'stemness'.
Yi R, Poy MN, Stoffel M, Fuchs E. Nature. 2008 Mar 13;452(7184):225-9. Epub 2008 Mar 2.
Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs.
Yi R, O'Carroll D, Pasolli HA, Zhang Z, Dietrich FS, Tarakhovsky A, Fuchs E. Nat Genet. 2006 Mar;38(3):356-62. Epub 2006 Feb 5.
Overexpression of exportin 5 enhances RNA interference mediated by short hairpin RNAs and microRNAs.
Yi R, Doehle BP, Qin Y, Macara IG, Cullen BR. RNA. 2005 Feb;11(2):220-6. Epub 2004 Dec 21.
Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha.
Zeng Y, Yi R, Cullen BR. EMBO J. 2005 Jan 12;24(1):138-48. Epub 2004 Nov 25.
Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs.
Yi R, Qin Y, Macara IG, Cullen BR. Genes Dev. 2003 Dec 15;17(24):3011-6. Epub 2003 Dec 17.
MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms.
Zeng Y, Yi R, Cullen BR. Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9779-84. Epub 2003 Aug 5.
Both ran and importins have the ability to function as nuclear mRNA export factors.
Yi R, Bogerd HP, Wiegand HL, Cullen BR. RNA. 2002 Feb;8(2):180-7.
Recruitment of the Crm1 nuclear export factor is sufficient to induce cytoplasmic expression of incompletely spliced human immunodeficiency virus mRNAs.
Yi R, Bogerd HP, Cullen BR. J Virol. 2002 Mar;76(5):2036-42.