Biomolecular Networks Laboratories

RNA Biofunction Laboratory

Prof. HIROSE Tetsuro Prof. HIROSE Tetsuro


Non-coding RNA (ncRNA), Phase separation, Membraneless organelle, Stress response, Disease

We study the architectural function of non-coding RNAs to build intracellular structures.

Transcriptome analysis has revealed that large portions of eukaryotic genomes produce numerous non-coding RNAs (ncRNAs), which expectedly play important regulatory roles in various biological processes. Our goal is to elucidate the functions of these ncRNAs and reveal the underlying new genetic code, thereby redefining the basic concept of genome function. We recently found that ncRNAs play architectural roles in membraneless organelles. Now we are studying the mode of action and cellular function of these ncRNAs using basic molecular and cellular experimental techniques combined with biophysical and bioinformatic tools.

Architectural ncRNA can construct membraneless organelles through phase separation. The ncRNAs harbor distinct functional domains to function as chromatin hubs and reaction crucibles for specific biochemical reactions, particularly in the nucleus.
Images: Paraspeckle as an ncRNA-dependent membraneless organelle detected by a confocal microscope (left), a super-resolution microscope (middle) and an electron microscope (right).


Tetsuro Hirose (Professor) hirose[at]
Tomohiro Yamazaki (Associate Professor) tyamazaki[at]
Kensuke Ninomiya (Associate Professor) k-ninomiya[at]
Ichiro Taniguchi (Assistant Professor) taniguchi.ichiro.fbs[at]
Kanako Kita (Assistant Professor, Graduate School of Medicine)  
Naoko Fujiwara (Researcher)  
Miwako Okamura (Technical Assistant)  
Rieko Takahashi (Technical Assistant)  
Junko Fujita (Secretary)  
Hiroko Yasui (Secretary)  

You could probably reach more information of individual researchers by Research Map and researcher's search of Osaka-U.

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What is your hot research topic?
  1. Decoding the ncRNA code
  2. Mechanism of phase separation or transition induced by ncRNA
  3. Mechanism of ncRNA bodies-chromatin intereactions
  4. Function of genomic repetitive elements
  5. Acquisition mechanism of species-specific traits
What is your breakthrough or research progress in the last 5 years?
Our group discovered a novel ncRNA function that works as a structural scaffold of membraneless organelles. The ncRNA can sequestrate multiple proteins with intrinsically disordered domains, thereby inducing liquid-liquid phase separation that is a driving force to construct the massive membraneless organelles. Multiple ncRNAs with the similar function were additionally identified as products of the human genome. Based on these results, we proposed to term these ncRNAs “architectural ncRNAs” as a new functional subcategory in ncRNAs.
What kind of background do your lab members have?
Our group members with various backgrounds join the laboratory after graduation of Faculty of Science, Engineering, Agriculture or Medicine.
Do you collaborate with other institutions and universities?
Our group has been collaborating with a number of laboratories in Japan (Hokkaido Univ., Univ. of Tokyo, AIST and RIKEN) as well as in foreign countries (CNRS in FR, MPI in DEU, Fraincis Crick Inst in UK, Univ. of Rochester in USA, Univ. of Western Australia in AUS and KAUST in SA)
What kind of careers do your Lab's alumni go on to?
Many of the former laboratory members successfully got the academic positions (e.g. Kumamoto Univ., Ritsumeikan Univ., NCGH and Univ. of Arizona) and the researcher position in bio-venture company.
How do you develop your research?
Understanding ncRNA functions and decoding the ncRNA code will reconstruct the basic concept on the mode of the genome functions and also facilitate the research by new perspective to understand the mechanism of various physiological events and diseases.
Recent Representative Publications
Hirose et al. (2022) Nat Rev Mol Cell Biol.
Ninomiya et al. (2021) EMBO J. 40, e107976
Yamazaki et al. (2021) EMBO J. 40, e107270
Ninomiya et al. (2020) EMBO J. 39, e102729
Yamazaki et al. (2018) Mol. Cell 70, 1038-1053
Chujo et al. (2017) EMBO J. 30, 1447-1462
Mannen et al. (2016) J. Cell Biol. 214, 45-59
Kawaguchi et al. (2015) PNAS 112, 4304-4309

Research Highlights

Publications (Research Articles, Reviews, Books)


Fukumura K, Yoshimoto R, Sperotto L, Kang HS, Hirose T, Inoue K, Sattler M, Mayeda A.

SPF45/RBM17-dependent, but not U2AF-dependent, splicing in a distinct subset of human short introns

Nat Commun. 12(1):4910  2021

Yamazaki T, Hirose T.

Control of condensates dictates nucleolar architecture

Science. 373(6554):486-487  2021

Ninomiya K, Iwakiri J, Aly MK, Sakaguchi Y, Adachi S, Natsume T, Terai G, Asai K, Suzuki T, Hirose T.

m6A modification of HSATIII lncRNAs regulates temperature-dependent splicing

EMBO J. 40(15) e107976  2021 PMID:34184765 DOI:10.15252/embj.2021107976

Nakagawa S, Yamazaki T, Mannen T, Hirose T.

ArcRNAs and the formation of nuclear bodies

Mamm genome.   2021 DOI:10.1007/s00335-021-09881-5

Yamazaki T, Yamamoto T, Yoshino H, Souquere S, Nakagawa S, Pierron G, Hirose T.

Paraspeckles are constructed as block copolymer micelles

EMBO J. 40(12) e107270  2021 PMID:33885174 DOI:10.15252/embj.2020107270

Shibata T, Nagano K, Ueyama M, Ninomiya K, Hirose T, Nagai Y, Ishikawa K, Kawai G, Nakatani K.

Small molecule targeting r(UGGAA)n disrupts RNA foci and alleviates disease phenotype in Drosophila model

Nat Commun. 12(1):236-236  2021 PMID:33431896 DOI:10.1038/s41467-020-20487-4

Yamazaki T, Hirose T.

CRISPR-Mediated Mutagenesis of Long Noncoding RNAs

Methods Mol Biol. 2254:283-303  2021 PMID:33326083 DOI:10.1007/978-1-0716-1158-6_18


Gidlöf O, Bader K, Celik S, Grossi M, Nakagawa S, Hirose T, Metzler B, Olde B, Erlinge D.

Inhibition of the long non-coding RNA NEAT1 protects cardiomyocytes from hypoxia in vitro via decreased pri-miRNA processing

Cell Death Dis. 11(8):677  2020 PMID:32826883 DOI:10.1038/s41419-020-02854-7

Ramilowski JA, Yip CW, Agrawal S, Chang JC, Ciani Y, Kulakovskiy IV, Mendez M, Ooi JLC, Ouyang JF, Parkinson N, Petri A, Roos L, Severin J, Yasuzawa K, Abugessaisa I, Akalin A, Antonov IV, Arner E, Bonetti A, Bono H, Borsari B, Brombacher F, Cameron CJ, Cannistraci CV, Cardenas R, Cardon M, Chang H, Dostie J, Ducoli L, Favorov A, Fort A, Garrido D, Gil N, Gimenez J, Guler R, Handoko L, Harshbarger J, Hasegawa A, Hasegawa Y, Hashimoto K, Hayatsu N, Heutink P, Hirose T, Imada EL, Itoh M, Kaczkowski B, Kanhere A, Kawabata E, Kawaji H, Kawashima T, Kelly ST, Kojima M, Kondo N, Koseki H, Kouno T, Kratz A, Kurowska-Stolarska M, Kwon ATJ, Leek J, Lennartsson A, Lizio M, L?pez-Redondo F, Luginb?hl J, Maeda S, Makeev VJ, Marchionni L, Medvedeva YA, Minoda A, M?ller F, Mu?oz-Aguirre M, Murata M, Nishiyori H, Nitta KR, Noguchi S, Noro Y, Nurtdinov R, Okazaki Y, Orlando V, Paquette D, Parr CJC, Rackham OJL, Rizzu P, S?nchez Martinez DF, Sandelin A, Sanjana P, Semple CAM, Shibayama Y, Sivaraman DM, Suzuki T, Szumowski SC, Tagami M, Taylor MS, Terao C, Thodberg M, Thongjuea S, Tripathi V, Ulitsky I, Verardo R, Vorontsov IE, Yamamoto C, Young RS, Baillie JK, Forrest ARR, Guig? R, Hoffman MM, Hon CC, Kasukawa T, Kauppinen S, Kere J, Lenhard B, Schneider C, Suzuki H, Yagi K, de Hoon MJL, Shin JW, Carninci P.

Functional annotation of human long noncoding RNAs via molecular phenotyping

Genome Res. 30(7):1060-1072  2020 PMID:32718982 DOI:10.1101/gr.254219.119

Liang S, Takahashi H, Hirose T, Kuramitsu Y, Hatakeyama S, Yoshiyama H, Wang R, Hamada JI, Iizasa H.

NONO Is a Negative Regulator of SOX2 Promoter

Cancer Genomics Proteomics. 17(4):359-367  2020 PMID:32576581 DOI:10.21873/cgp.20195

Kukharsky MS, Ninkina NN, An H, Telezhkin V, Wei W, Meritens CR, Cooper-Knock J, Nakagawa S, Hirose T, Buchman VL, Shelkovnikova TA

Long non-coding RNA Neat1 regulates adaptive behavioural response to stress in mice

Transl Psychiatry 10(1):171-171  2020 PMID:32467583 DOI:10.1038/s41398-020-0854-2

Yamamoto T , Yamazaki T , Hirose T .

Phase separation driven by production of architectural RNA transcripts

Soft Matter. 16(19):4692-4698  2020 PMID:32396591 DOI:10.1039/c9sm02458a

Suzuki E, Ogawa N, Takeda TA, Nishito Y, Tanaka YK, Fujiwara T, Matsunaga M, Ueda S, Kubo N, Tsuji T, Fukunaka A, Yamazaki T, Taylor KM, Ogra Y, Kambe T.

Detailed analyses of the crucial functions of Zn transporter proteins in alkaline phosphatase activation

Journal of Biological Chamistry 295(17):5669-5684  2020 PMID:32179649 DOI:10.1074/jbc.RA120.012610

Our ideal candidate (as a graduate student)

We are looking for a highly motivated person to work on our research topics as our lab member. Our lab welcomes the person who loves taking care of creatures, hand working and handcraft too. Any kind of background (such as your expertise or major) is available.


RNA Biofunction Laboratory, Graduate School of Frontier Biosciences, Osaka University,
1-3 Yamadaoka, Suita, Osaka 565-0871 Japan.

TEL: +81-6-6879-4675

E-mail: hirose[at] (Prof. Tetsuro Hirose)

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