Makoto Komiyama

Publications (2)13.92 Total impact

• Article: Structure, function and targeting of human telomere RNA.

  Yan Xu, Makoto Komiyama
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  ABSTRACT: Human telomeres play an important role in critical processes underlying genome stability, cancer, and aging. For a long time, telomeres have been considered transcriptionally silent. A recent finding demonstrated that telomere DNA is transcribed into telomeric repeat-containing RNA (referred to as TERRA) in mammalian cells. The existence of TERRA RNA may reveal a new level of regulation and protection of chromosome ends that could promote valuable insight into fundamental biological processes such as cancer and aging. Revealing the structure and function of telomere RNA will be essential for understanding telomere biology and telomere-related diseases. NMR and X-ray crystallography have demonstrated that human telomere RNA forms G-quadruplex structures. More recently, human telomere RNA is suggested to form a G-quadruplex dimer in the living cells by employing a light-switching probe. The proposed structures may be a valuable target for anticancer agents directed against telomeres. This review highlights the structures and topologies for telomere RNA G-quadruplex and recent efforts in the design of telomere RNA G-quadruplex ligands. The future challenges in the field are outlined.
  Methods 03/2012; 57(1):100-5. · 4.01 Impact Factor
• Article: Inhibition of translation by small RNA-stabilized mRNA structures in human cells.

  Kenichiro Ito, Sou Go, Makoto Komiyama, Yan Xu
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  ABSTRACT: RNA-mediated gene regulation and expression are critically dependent on both nucleic acid architecture and recognition. We present a novel mechanism for the regulation of gene expression through direct RNA-RNA interactions between small RNA and mRNA in human cells. Using mRNA reporters containing G-rich sequences in the 5'-untranslated region (5'-UTR), in the coding region, or both, we showed that G-rich small RNAs bind to the reporter mRNAs and form an intermolecular RNA G-quadruplex that can inhibit gene translation in living cells. Using a combination of circular dichroism (CD) and RNase footprinting in vitro, we found that the intermolecular G-quadruplexes show a parallel G-quadruplex structure. We next investigated whether the intermolecular G-quadruplex is present in living cells. Employing the fluorophore-labeled probes, we found that two G-rich RNA molecules form an intermolecular G-quadruplex structure in living cells. These results extend the concept of small RNA-mediated expression and suggest an important role for such RNA structures in the inhibition of mRNA translation.
  Journal of the American Chemical Society 11/2011; 133(47):19153-9. · 9.91 Impact Factor