Laboratory of RNA biofunction
Graduate School of Frontier Biosciences
Professor

Tetsuro HIROSE

hirose.tetsuro.fbs

Specially Appointed Associate Professor

Tomohiro YAMAZAKI

yamazaki.tomohiro.fbs

Specially Appointed Associate Professor

Kensuke NINOMIYA

ninomiya.kensuke.fbs

URL: http://hirose-lab.com/
Post-genome analysis at the beginningof 21st century revealed that large
numbers of non-coding RNAs (ncRNAs)
are produced from the large noncoding regions of the genome, andtheir functions have attracted
considerable attention. Our laboratory
aims to reconstruct the concept ofgenome function by clarifying thebiological functions of these ncRNAs
and elucidating new genetic code rulesthat govern their functions. In particular,
we are studying the formation
mechanism of intracellular structuresand its role controlled by the ncRNA
mediated phase separation
phenomenon, which we have revealed
so far, by incorporating biophysical andbioinformatics methods into basic
molecular and cell biological studies.
Decoding of non-coding RNA
codes
Only 2% of the human genome encodes
protein information. And the remaining 98%
non-coding region produces tens of
thousands of different ncRNAs (Figure 1).
The protein-coding genes work according toa textbook genetic code, however, this codeworks for only 2% of the genome. On theother hand, what sequence rules (or geneticcode) are necessary for ncRNAs to function
remains a mystery. Therefore, ourlaboratory is working to decipher the new
genetic code that governs the function ofncRNAs. ncRNAs, without exception, form
complexes with multiple RNA-binding
proteins (RBPs) to form an operating
apparatus. In order to decipher a new
genetic code (ncRNA code) that specifiesncRNA functions, we are trying to clarify
what kind of ncRNA sequences andstructures are recognized by the RBPs thatform the ncRNA machinery, and how suchsequences were acquired during evolution.

Analysis of non-coding RNA-induced
intracellular phase separation
As a function specified by the ncRNA code,
we focus on the function of ncRNAs to build
intracellular structures. In the nucleus of
eukaryotic cells, there are many
membraneless structures that fulfill importantfunctions (Fig. 2). Our research has revealed
that some of these structures are constructed Figure 1. Post-genome analyses have revealed that tens ofusing ncRNAs as a structural scaffolds (Fig. thousands of ncRNAs are produced from non-coding regions thatmake up 98% of the human genome. Their functions remain
largely unknown.
3). Recently, it has been found that thesemembraneless structures have droplet or gellike properties and are formed by a physicalphenomenon called "liquid-liquid phaseseparation (LLPS). In other words, ncRNAs
seem to act as seed molecules that induce
LLPS in the nuclear space. Therefore, we aretrying to understand how the massive andordered membraneless structures are formed
through LLPS, especially to elucidate theFigure 2: Schematic diagram of membranelessfunctions of intrinsically disordered proteinsstructures in mammalian cell nuclei
directly responsible for LLPS and to decipher
the ncRNA code to consolidate these proteins.
Research on the significance of
intracellular phase separation
LLPS is a clever mechanism forcompartmentalizing intracellular space
without the use of membranes (Figure 3).
What is happening in the structure formedby LLPS? What is the significance of using
RNA molecules as a structural scaffolds? We
are trying to elucidate LLPS-related
intracellular phenomena throughunderstanding the ncRNA functions.

Figure 3. ncRNAs gather a group of intrinsicallydisordered proteins to induce LLPS and form
membraneless structures. Three regulatory functions
have been proposed for the membraneless structures:reaction crucible, molecular sponge, and structural hub.

RNA research has rewritten thefundamental rules of biology andset new research trends. In thiscentury, a new RNA world full ofmysteries has emerged. We
welcome romantic and energetic
students who are willing tochallenge this mystery.

Graduate School of Frontier Biosciences,
Osaka University , 1-3 Yamadaoka, Suita, Osaka
565-0871, Japan
TEL: +81-6-6879-4675
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