The Fukunaga lab investigates the mechanism and biology of post-transcriptional gene regulation controlled by RNA-binding proteins and small silencing RNAs. Our research projects will answer fundamental biological questions and also potentially lead to therapeutic applications to human disease.
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 and spermatogenesis as model systems since post-transcriptional gene regulation is particularly important during these processes.
We use a combination of biochemistry, biophysics, Drosophila genetics, cell culture, and next-generation sequencing, in order to understand important biological questions from the atomic to the organismal level.
Publications
Zhu L, Fukunaga R. RNA-binding protein Maca is crucial for gigantic male fertility factor gene expression, spermatogenesis, and male fertility, in Drosophila. PLoS Genetics. 17, e1009655, (2021)
Vakrou S, Liu Y, Zhu L, Greenland GV, Simsek B, Hebl BV, Guan Y, Woldemichael K, Talbot CC, Aon MA, Fukunaga R, Abraham MR. Differences in molecular phenotype in mouse and human hypertrophic cardiomyopathy. Scientific Reports. 11, 13163, (2021)
Liu Y, Afzal J, Vakrou S, Greenland GV, Talbot CC Jr, Hebl VB, Guan Y, Karmali R, Tardiff JC, Leinwand LA, Olgin JE, Das S, Fukunaga R, Abraham MR. Differences in microRNA-29 and Pro-fibrotic Gene Expression in Mouse and Human Hypertrophic Cardiomyopathy. Front Cardiovasc Med. 6,170, (2019)
Zhu L, Liao ES, Fukunaga R. Drosophila Regnase-1 RNase is required for mRNA and miRNA profile remodeling during larva-to-adult metamorphosis. RNA Biology 16, 1386-1400, (2019)
Zhu L, Liao ES, Ai Y, Fukunaga R. RNA methyltransferase BCDIN3D is crucial for female fertility and miRNA and mRNA profiles in Drosophila ovaries. PLoS ONE 14, e0217603, (2019)
Liao ES, Kandasamy SK, Zhu L, Fukunaga R. DEAD-box RNA helicase Belle post-transcriptionally promotes gene expression in an ATPase activity-dependent manner. RNA 25, 825-839, (2019)
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, 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 Acids Res., 46, 3726-3741, (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, 14031-14036, (2016)
Lin X, Steinberg S, Kandasamy S, Afzal J, Mbiyangandu B, Liao ES, 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, e0156065, (2016)
Fukunaga R, Colpan C, Han BW, Zamore PD. Inorganic phosphate blocks binding of pre-miRNA to Dicer-2 via its PAZ domain. EMBO Journal, 18, 371-384, (2014)
Fukunaga R, Han BW, Hung JH, Xu J, Weng Z, Zamore PD. Dicer Partner Proteins Tune the Length of Mature miRNAs in Flies and Mammals. Cell, 151, 533-546, (2012)
Vaniya A, Karlstaedt A, Gulkok D, Thottakara T, Liu Y, Fan S, Eades H, Vakrou S, Fukunaga R, Vernon H, Fiehn O , Abraham R. Allele-specific dysregulation of lipid and energy metabolism in early-stage hypertrophic cardiomyopathy. J Mol Cell Cardiol Plus. 8:100073 (2024)
Azlan A, Zhu L, Fukunaga R. Female-germline specific protein Sakura interacts with Otu and is crucial for germline stem cell renewal and differentiation and oogenesis. BioRxiv https://doi.org/10.1101/2024.10.04.616675. eLife https://elifesciences.org/reviewed-preprints/103828
Taira Y, Zhu L, Fukunaga R. RNA-binding protein Miso/CG44249 is crucial for minor splicing during oogenesis in Drosophila. RNA. 31(6):822-835 (2025)
