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Dissecting the role of mRNA decay in the maintenance of homeostatsis

Keiji Kuba (photo)

Keiji Kuba

Research Site Akita University Graduate School of Medicine
Department of Biochemistry and Metabolic Science
Professor

Content

In gene expression, DNA is transcribed to RNA and then translated to protein, whereas untranscribed RNA is degraded, so called mRNA decay, and provide nucleotide sources for newly synthesizing RNA. While various mechanisms for regulating mRNA decay have been elucidated, the significance and role of mRNA decay remains elusive. In this study we aim to dissect the roles of mRNA decay in gene expression and nucleotide metabolism thereby elucidating unknown interactions between biological systems underlying the dynamic maintenance of homeostasis. The outcomes of this study should give novel concepts to the diagnosis and therapy for cancer, cardiovascular and infectious diseases.

Publication

  1. Sato T, Sato C, Kadowaki A, Watanabe H, Ho L, Ishida J, Yamaguchi T, Kimura A, Fukamizu A, Penninger JM, Reversade B, Ito H, Imai Y, Kuba K. ELABELA - APJ axis protects from pressure overload heart failure and Angiotensin II-induced cardiac damage. Cardiovasc Res, in press.
  2. Kimura H, Eguchi S, Sasaki J, Kuba K, Nakanishi H, Takasuga S, Yamazaki M, Goto A, Watanabe H, Itoh H, Imai Y, Suzuki A, Mizushima N, Sasaki T. Vps34 regulates myofibril proteostasis to prevent hypertrophic cardiomyopathy. JCI Insight. 2: e89462, 2017.
  3. Yang CY, Ramamoorthy S, Boller S, Rosenbaum M, Rodriguez Gil A, Mittler G, Imai Y, Kuba K, Grosschedl R. Interaction of CCR4-NOT with EBF1 regulates gene-specific transcription and mRNA stability in B lymphopoiesis. Genes Dev. 30: 2310-2324, 2016.
  4. Demetz E, Schroll A, Auer K, Heim C, Patsch JR, Eller P, Theurl M, Theurl I, Theurl M, Seifert M, Lener D, Stanzl U, Haschka D, Asshoff M, Dichtl S, Nairz M, Huber E, Stadlinger M, Moschen AR, Li X, Pallweber P, Scharnagl H, Stojakovic T, Mä rz W, Kleber ME, Garlaschelli K, Uboldi P, Catapano AL, Stellaard F, Rudling M, Kuba K, Imai Y, Arita M, Schuetz JD, Pramstaller PP, Tietge UJ, Trauner M, Norata GD, Claudel T, Hicks AA, Weiss G, Tancevski I. The arachidonic acid metabolome serves as a conserved regulator of cholesterol metabolism. Cell Metab. 20: 787-798, 2014.
  5. Sato T, Suzuki T, Watanabe H, Kadowaki A, Fukamizu A, Liu PP, Kimura A, Ito H, Penninger JM, Imai Y, Kuba K. Apelin is a positive regulator of ACE2 in failing hearts. J Clin Invest. 123: 5203-5211, 2013.
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