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Autophagy induction promoted by m6A reader YTHDF3 through translation upregulation of FOXO3 mRNA.
Hao, WeiChao; Dian, MeiJuan; Zhou, Ying; Zhong, QiuLing; Pang, WenQian; Li, ZiJian; Zhao, YaYan; Ma, JiaCheng; Lin, XiaoLin; Luo, RenRu; Li, YongLong; Jia, JunShuang; Shen, HongFen; Huang, ShiHao; Dai, GuanQi; Wang, JiaHong; Sun, Yan; Xiao, Dong.
Afiliação
  • Hao W; Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, 510080, Guangzhou, China.
  • Dian M; Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
  • Zhou Y; Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, China.
  • Zhong Q; Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, 510515, Guangzhou, China.
  • Pang W; Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
  • Li Z; Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, 510515, Guangzhou, China.
  • Zhao Y; Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
  • Ma J; Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
  • Lin X; Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
  • Luo R; Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, 510080, Guangzhou, China.
  • Li Y; Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, 10084, Beijing, China.
  • Jia J; Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
  • Shen H; Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, 510315, Guangzhou, China.
  • Huang S; School of Medicine, Shenzhen Campus of Sun Yat-sen University, 518107, Guangdong, China.
  • Dai G; Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
  • Wang J; Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, 510515, Guangzhou, China.
  • Sun Y; Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
  • Xiao D; Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
Nat Commun ; 13(1): 5845, 2022 10 04.
Article em En | MEDLINE | ID: mdl-36195598
Autophagy is crucial for maintaining cellular energy homeostasis and for cells to adapt to nutrient deficiency, and nutrient sensors regulating autophagy have been reported previously. However, the role of eiptranscriptomic modifications such as m6A in the regulation of starvation-induced autophagy is unclear. Here, we show that the m6A reader YTHDF3 is essential for autophagy induction. m6A modification is up-regulated to promote autophagosome formation and lysosomal degradation upon nutrient deficiency. METTL3 depletion leads to a loss of functional m6A modification and inhibits YTHDF3-mediated autophagy flux. YTHDF3 promotes autophagy by recognizing m6A modification sites around the stop codon of FOXO3 mRNA. YTHDF3 also recruits eIF3a and eIF4B to facilitate FOXO3 translation, subsequently initiating autophagy. Overall, our study demonstrates that the epitranscriptome regulator YTHDF3 functions as a nutrient responder, providing a glimpse into the post-transcriptional RNA modifications that regulate metabolic homeostasis.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autofagia Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autofagia Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China País de publicação: Reino Unido