TY - JOUR
T1 - Control of tissue size and development by a regulatory element in the yorkie 3'UTR
AU - Umegawachi, Takanari
AU - Yoshida, Hideki
AU - Koshida, Hiromu
AU - Yamada, Momoko
AU - Ohkawa, Yasuyuki
AU - Sato, Tetsuya
AU - Suyama, Mikita
AU - Krause, Henry M.
AU - Yamaguchi, Masamitsu
N1 - Funding Information:
We are very grateful to E.R. Gavis, N. Naka-shima, A. Nakamura and H. McNeill for providing reagents, K. Usui for technical assistance and A. Ephrussi for helpful discussions. We also thank the Drosophila Genomics Resour-ce Center for providing the NIH 2P40OD0-10949-10A cultured cell line. RNA-seq analy-sis was performed in the Cooperative Rese-arch Project Program of the Medical Institute of Bioregulation, Kyushu University. This work was supported in part by grants to H.Y. from the Suzuken Memorial Foundation, The Ue-hara Memorial Foundation, Takeda Science Foundation, Inamori Foundation, Japan Society for the Promotion of Science (JSPS) (Grant Number 26440097) and the JSPS Core-to-Core Program, Asia-Africa Science Platforms, to H.M.K. by the Canadian Institutes of Health Research, and to T.U from The Japan Science Society.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
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M3 - Article
AN - SCOPUS:85016234601
SN - 2156-6976
VL - 7
SP - 673
EP - 687
JO - American Journal of Cancer Research
JF - American Journal of Cancer Research
IS - 3
ER -
