Laboratories

RNA Molecular Medicine

Prof. Okamura
Professor
Katsutomo OKAMURA
Assistant Professor
Ren SHIMAMOTO

Outline of Research and Education

Advances in genomics technologies have transformed research and development strategies in biology and biomedicine, allowing us to access genetic information encoded in our DNA (Fig 1). Our laboratory is interested in understanding how individual genes form large regulatory networks to control biological processes. In particular, we study how regulatory non-coding RNAs including microRNAs (miRNAs) contribute to gene regulation and how their misregulation leads to human health problems.

Research in our laboratory relies on a combination of traditional and modern techniques including biochemistry, genetics and computational biology. Students are expected to learn how to carefully interpret analysis results and develop strategies to answer biological questions by exploiting existing technologies or devising new techniques.

Major Research Topics

How is expression of miRNAs controlled?

We have witnessed a paradigm shift in research of gene regulation, and the importance of post-transcriptional regulation of protein-coding genes has now been broadly recognized. Expression of miRNAs should also be regulated at multiple levels (Fig 2). Precise regulation of miRNA levels is important because misregulation of miRNAs often results in human disease. We study how miRNA levels are controlled under healthy and disease conditions using genomics and biochemical techniques, and examine their biological significance at the cellular and organismal levels (Fig 3).

Why are there many ways to produce miRNAs?

We discovered novel mechanisms of miRNA processing that use machineries known to produce other RNA families, such as mRNA introns and ribosomal RNAs (Fig 2). This means that RNA processing machineries often have unexpected roles in gene regulation. We study the biological significance of non-canonical roles of various RNA processing pathways.

How have small RNA pathways changed in evolution?

Our previous studies revealed a variety of small RNA pathways including those that are only present in particular organisms functioning as natural defense systems (Fig 2). To capture the full diversity of animal small RNA pathways, we are sequencing small RNAs from various animals by next generation sequencing. Discoveries of new small RNA pathways may pave the way for the development of novel technologies that complement the current CRISPR or RNA interference technologies.

References

  1. Zhou and Lim et al., eLife, 7, e38389, 2018
  2. Goh and Okamura, Methods Mol Biol., 1680, 41-63, 2018
  3. Lim and Ng et al., Cell Reports, 15 (8), 1795–1808, 2016
  4. Chak et al., RNA, 21(3), 375-384, 2015
  5. Pek and Okamura, WIREs RNA, 6, 671-86, 2015
  6. Chak and Okamura, Frontiers in Genetics, 5, 172, 2014
  7. Okamura et al., Genes & Dev, 27(7), 778-92, 2013
  8. Okamura, WIREs RNA, 3, 351–368, 2012
  9. Okamura et al., Molecular Cell., 36(3), 431-44, 2009
  10. Okamura et al., Nature, 453(7196), 803-6, 2008
  11. Okamura et al., Cell, 130(1), 89-100, 2007
Fig.1
Fig.1 Gene regulatory networks and their importance in normal development and physiology.
Fig.2
Fig.2 microRNA processing pathway.
Fig.3
Fig.3 Outline of research strategies.
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