Control of tissue size and development by a regulatory element in the yorkie 3'UTR

Takanari Umegawachi, Hideki Yoshida, Hiromu Koshida, Momoko Yamada, Yasuyuki Ohkawa, Tetsuya Sato, Mikita Suyama, Henry M. Krause, Masamitsu Yamaguchi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Regulation of the Hippo pathway via phosphorylation of Yorkie (Yki), the Drosophila homolog of human Yes-associated protein 1, is conserved from Drosophila to humans. Overexpression of a non-phosphorylatable form of Yki induces severe overgrowth in adult fly eyes. Here, we show that yki mRNA associates with microsomal fractions and forms foci that partially colocalize to processing bodies in the vicinity of endoplasmic reticulum. This localization is dependent on a stem-loop (SL) structure in the 3' untranslated region of yki. Surprisingly, expression of SL deleted yki in eye imaginal discs also results in severe overgrowth phenotypes. When the structure of the SL is disrupted, Yki protein levels increase without a significant effect on RNA levels. When the SL is completely removed, protein levels drastically increase, but in this case, due to increased RNA stability. In the latter case, we show that the increased RNA accumulation is due to removal of a putative miR-8 seed sequence in the SL. These data demonstrate the function of two novel regulatory mechanisms, both controlled by the yki SL element, that are essential for proper Hippo pathway mediated growth regulation.

Original languageEnglish
Pages (from-to)673-687
Number of pages15
JournalAmerican Journal of Cancer Research
Volume7
Issue number3
Publication statusPublished - Jan 1 2017

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Umegawachi, T., Yoshida, H., Koshida, H., Yamada, M., Ohkawa, Y., Sato, T., Suyama, M., Krause, H. M., & Yamaguchi, M. (2017). Control of tissue size and development by a regulatory element in the yorkie 3'UTR. American Journal of Cancer Research, 7(3), 673-687.