Ribosome biogenesis is an essential cellular process that must meet the demands of normal cell growth and stress responses. The foundation of ribosome biogenesis is the synthesis of ribosomal RNA. In this process, ribosomal RNA is captured, chemically modified, cleaved, and released by small nucleolar ribonucleoprotein particles (snoRNPs). Studies in my laboratory over the years suggest an emerging principle in which the single act of rRNA capture by snoRNPs encompasses multiple coordinated events occurring simultaneously with catalysis at locations distal from the active site. The multi-component yet tractable H/ACA snoRNPs offer a prototypical system for examining these interactions in detail. Our goals are to establish a mechanistic view of ribosomal RNA capture and release by snoRNPs from the initial docking through the end of chemical reactions. The proposed studies will also provide an understanding of RNA-protein composite enzymes in general at atomic details. Cancerous cells display increased ribosome synthesis. Identifying signals that inhibit or promote ribosome synthesis will potentially reveal promising targets for therapy against tumor growth. The increasing evidence that 5-fluorouracil (5-FU) is incorporated into functional RNAs necessitates investigation of its role in inhibiting ribosomal RNA synthesis by blocking pseudouridylases. Human telomerase is a specialized H/ACA RNP that exploits the H/ACA RNA domain for its localization and maturation. The genetic disease dyskeratosis congenita (DC), which predisposes patients to epithelial cancers, results from mutations in telomerase RNA and two of the four core proteins in human H/ACA snoRNPs. Although defects in both ribosome biogenesis and telomere synthesis are observed in murine embryonic stem cells bearing DC mutants, a thorough understanding of how DC mutations affect the functioning of H/ACA snoRNPs will provide an understanding of the manner in which these mutations contribute to the pathology of DC.

Public Health Relevance

Cancerous cells display increased rate of ribosome synthesis. Identifying signals that inhibit or promote ribosome synthesis will potentially reveal promising targets for therapy against tumor growth.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Macromolecular Structure and Function C Study Section (MSFC)
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Preusch, Peter C
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Florida State University
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Li, Hong (2015) Structural Principles of CRISPR RNA Processing. Structure 23:13-20
Peng, Yu; Yu, Ge; Tian, Shaoxiong et al. (2014) Co-expression and co-purification of archaeal and eukaryal box C/D RNPs. PLoS One 9:e103096
Shao, Yaming; Li, Hong (2013) Recognition and cleavage of a nonstructured CRISPR RNA by its processing endoribonuclease Cas6. Structure 21:385-93
Zhou, Jing; Liang, Bo; Li, Hong (2011) Structural and functional evidence of high specificity of Cbf5 for ACA trinucleotide. RNA 17:244-50
Wang, Ruiying; Preamplume, Gan; Terns, Michael P et al. (2011) Interaction of the Cas6 riboendonuclease with CRISPR RNAs: recognition and cleavage. Structure 19:257-64
Xue, Song; Wang, Ruiying; Yang, Fangping et al. (2010) Structural basis for substrate placement by an archaeal box C/D ribonucleoprotein particle. Mol Cell 39:939-49
Zhou, Jing; Lv, Chao; Liang, Bo et al. (2010) Glycosidic bond conformation preference plays a pivotal role in catalysis of RNA pseudouridylation: a combined simulation and structural study. J Mol Biol 401:690-5
Zhou, Jing; Liang, Bo; Li, Hong (2010) Functional and structural impact of target uridine substitutions on the H/ACA ribonucleoprotein particle pseudouridine synthase. Biochemistry 49:6276-81
Liang, Bo; Zhou, Jing; Kahen, Elliot et al. (2009) Structure of a functional ribonucleoprotein pseudouridine synthase bound to a substrate RNA. Nat Struct Mol Biol 16:740-6
Carte, Jason; Wang, Ruiying; Li, Hong et al. (2008) Cas6 is an endoribonuclease that generates guide RNAs for invader defense in prokaryotes. Genes Dev 22:3489-96

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