Ryuya Fukunaga

Image of Dr. Ryuya Fukunaga

Ryuya Fukunaga

Assistant Professor
Primary Appointment: 
Biological Chemistry
410-955-3790

725 N. Wolfe Street
521A Physiology Bldg
Baltimore MD 21205

Research topic: 

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.

Selected Publications: 

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)

Yanagisawa T, Ishii R, Hikida Y, Fukunaga R, Sengoku T, Sekine SI, Yokoyama S, "A SelB/EF-Tu/aIF2γ-like protein from Methanosarcina mazei in the GTP-bound form binds cysteinyl-tRNACys." J. Struct. Funct. Genomics. 16, 25-41, (2015) 

Fukunaga R, Zamore PD. "A universal small molecule, inorganic phosphate, restricts the substrate specificity of Dicer-2 in small RNA biogenesis." Cell Cycle. 13(11):1671-6. (2014)

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, 371-84, (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, 533-46, (2012)

Cenik ES, Fukunaga R, Lu G, Dutcher R, Wang Y, Tanaka Hall TM, Zamore PD,  “Phosphate and R2D2 Restrict the Substrate Specificity of Dicer-2, an ATP-Driven Ribonuclease” Mol. Cell, 42, 172-84, (2011)

Fukunaga R, Doudna JA, “dsRNA with 5ў overhangs contributes to endogenous and antiviral RNA silencing pathways in plants” EMBO J., 28, 545-55, (2009)

Fukunaga R, Harada Y, Hirao I, Yokoyama S, “Phosphoserine aminoacylation of tRNA bearing an unnatural base anticodon” Biochem Biophys Res Commun., 1, 372, 480-5, (2008)

Fukunaga R, Yokoyama S, “Structural insights into the first step of RNA-dependent cysteine biosynthesis in archaea: crystal structure of Sep-tRNA:Cys-tRNA synthase from Archaeoglobus fulgidus” J. Mol. Biol., 29, 370, 128-41, (2007)

Fukunaga R, Yokoyama S, “The C-terminal domain of the archaeal leucyl-tRNA synthetase prevents misediting of isoleucyl-tRNAIle” Biochemistry, 1, 46, 4985-96, (2007)

Fukunaga R, Yokoyama S, “Structural insights into the first step of RNA-dependent cysteine biosynthesis in archaea. Structural basis of phosphoserine ligation to tRNA for genetic code evolution” Nat. Struct. Mol. Biol., 14, 272-9, (2007)

Fukunaga R, Yokoyama S, “Structure of the AlaX-M trans-editing enzyme from Pyrococcus horikoshii” Acta Crystallogr. D, 63, 390-400, (2007)

Fukunaga R, Yokoyama S, “Structural basis for substrate recognition by the editing domain of isoleucyl-tRNA synthetase” J. Mol. Biol. 359, 901-12, (2006)

Fukunaga R, Yokoyama S, “Aminoacylation complex structures of leucyl-tRNA synthetase and tRNALeu reveal two modes of discriminator base recognition for 3ў-end relocation toward the editing domain” Nat. Struct. Mol. Biol. 12, 915-922, (2005)

Fukunaga R, Yokoyama S, “Structural basis for non-cognate amino acid discrimination by the valyl-tRNA synthetase editing domain” J. Biol. Chem. 280, 29937-29945, (2005).

Fukunaga R, Yokoyama S, “Crystal Structure of Leucyl-tRNA Synthetase from the Archaeon Pyrococcus horikoshii Reveals a novel editing domain orientation” J. Mol. Biol. 346, 57-71, (2005).

Fukunaga R, Fukai S, Ishitani R, Nureki O, Yokoyama S, “Crystal Structures of the CP1 Domain from Thermus thermophilus Isoleucyl-tRNA synthetase and Its Complex with L-Valine” J. Biol. Chem. 279, 8396-8402, (2004)