Research

Since Nobel prize laureate Francis Crick has proposed in 1950s, the central dogma of life: DNA makes RNA makes protein, has been most basic principle in life. In our lab, we are investigating “translation” or a reaction from RNA to protein, which lies at the core of central dogma, focusing how translation is control, and how its control impacts on life.

Our genome has nearly 20,000 genes. They are not always turned on, rather controlled in time and space. It has been widely accepted that the on-off switch is generally controlled at transcription, or DNA to RNA, and that RNA just works simply as messenger of information from DNA to protein.

However, recent studies revealed that 1) the amount of RNA correlates only 30-40% of protein amount in cells, and that 2) RNA elements including frame-shift sites, alternative translation initiation codons, and stop-codon read-through produces diverse protein species from single RNA. These studies showed challenges to predict final output protein from RNA qualitatively and quantitatively, than as we previously thought. Moreover, the facts that 3) codon and/or amino acid sequences couples with ribosome stalling and protein synthesis regulation on ribosome and that 4) frequency of codon usage mediates RNA stability, provide the new idea; RNA codes more information beyond the triplet of nucleotide.

It is clear that translation is under more fine and complicated control than as we expected. However, although translation reaction has been known since 1950s, which RNAs are controlled, how the control is achieved, and how its regulation impacts on life has been poorly understood so far. Our laboratory is taking two major approaches and combine them to tackle the mystery of translation in cels.

Analysis with Next-Generation Sequencer

Recent development of next-generation deep sequencer allows us to identify and measure the RNA in cells. Using this technology, we are using ribosome profiling to understand which RNAs are translated and which codons are decoded by ribosome, surveying translation status in cells comprehensively.

Simultaneously, we also use the other deep-sequencing based technologies to investigate RNA-protein interaction, which regulates translation. Combining those techniques, we tackle to reveal ternary relationship among RNA, RNA-binding protein, and translation.

Also Classical Biochemical Methods

Translation is complicated and multistep reaction. Simultaneously, those steps are targets of regulation. To understand the mechanism of translation control, we need to dissect the reaction into fundamental processes. We used conventional but super powerful biochemistry to address molecular mechanism of RNA and its translation.