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Mechanism and biology of small silencing RNAs
The Fukunaga lab is broadly interested in RNA biology. More specifically, the Fukunaga lab investigates the mechanism and biology of post-transcriptional gene regulation controlled by small silencing RNAs and RNA-binding proteins. Our research projects will answer fundamental biological questions and also potentially lead to therapeutic applications to human disease.
For the small silencing RNA projects, we are particularly interested in the mechanisms by which the small silencing RNAs such as microRNAs (miRNAs) and small interfering RNAs (siRNAs) are produced by Dicer enzyme and by which the Dicer enzyme is regulated by Dicer-partner RNA-binding proteins in this small RNA biogenesis functions. Specifically, we aim to understand the molecular mechanism by which the length of small silencing RNAs produced by Dicer is defined and regulated, which is a biologically significant question.
For the RNA-binding proteins projects, we are interested in novel post-transcriptional gene regulation mechanism performed by uncharacterized or poorly characterized RNA-binding proteins. We use Drosophila oogenesis as one of the model systems since post-transcriptional gene regulation is particularly important during oogenesis.
We use a combination of biochemistry, biophysics, Drosophila genetics, cell culture, and next-generation sequencing, in order to understand RNA biology from the atomic to the organismal level.
Liao SE, Kandasamy SK, Zhu L, Fukunaga R. "DEAD-box RNA helicase Belle post-transcriptionally promotes gene expression in an ATPase activity-dependent manner”. RNA. 2019 Apr 12. pii: rna.070268.118
Zhu L, Kandasamy SK, Liao ES, Fukunaga R. "LOTUS domain protein MARF1 binds CCR4-NOT deadenylase complex to post-transcriptionally regulate gene expression in oocytes". Nature Communications, 9:4031 (2018)
Liao ES, Ai Y, Fukunaga R. "An RNA-binding protein Blanks plays important roles in defining small RNA and mRNA profiles in Drosophila testes". Heliyon, 4, e00706, (2018)
Vakrou S, Fukunaga R, Foster DB, Sorensen L, Liu Y, Guan Y, Woldemichael K, Pineda-Reyes R, Liu T, Jill C. Tardiff JC, Leinwand LA, Tocchetti CG, Abraham TP, Brian O’Rourke B, Aon MA, Abraham MR. "Allele-specific differences in transcriptome, miRNome, and mitochondrial function in two hypertrophic cardiomyopathy mouse models”. JCI Insight. 3(6): e94493 (2018)
Fukunaga R. "Dicer-2 partner protein Loquacious-PD allows hairpin RNA processing into siRNAs in the presence of inorganic phosphate”. Biochemical and Biophysical Research Communications. 498: 1022–1027 (2018)
Zhu L, Kandasamy SK, Fukunaga R. "Dicer partner protein tunes the length of miRNAs using base-mismatch in the pre-miRNA stem” Nucleic Acid Research, 46, 3726-3741, (2018)
Liao SE, Fukunaga R. "Kinetic Analysis of Small Silencing RNA Production by Human and Drosophila Dicer Enzymes In Vitro." Methods Mol Biol. 1680:101-121 (2018)
Kandasamy SK, Zhu L, Fukunaga R. "The C-terminal dsRNA-binding domain of Drosophila Dicer-2 is crucial for efficient and high-fidelity production of siRNA and loading of siRNA to Argonaute2." RNA, 23, 1139-1153, (2017)
Kandasamy SK, Fukunaga R. "Phosphate-binding pocket in Dicer-2 PAZ domain for high-fidelity siRNA production." Proc. Natl. Acad. Sci. U S A. 113(49):14031-14036, (2016)
Lin X, Steinberg S, Kandasamy S, Afzal J, Mbiyangandu B, Liao S, Guan Y, Corona-Villalobos C, Matkovich S, Epstein N, Tripodi D, Huo Z, Cutting G, Abraham T, Fukunaga R, Abraham R "Common MiR-590 Variant rs6971711 present only in African Americans reduces miR-590 biogenesis." PLoS ONE. 11(5): e0156065. (2016)