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Angiogenin-cleaved tRNA halves interact with cytochrome c, protecting cells from apoptosis during osmotic stress.
Saikia, Mridusmita; Jobava, Raul; Parisien, Marc; Putnam, Andrea; Krokowski, Dawid; Gao, Xing-Huang; Guan, Bo-Jhih; Yuan, Yiyuan; Jankowsky, Eckhard; Feng, Zhaoyang; Hu, Guo-fu; Pusztai-Carey, Marianne; Gorla, Madhavi; Sepuri, Naresh Babu V; Pan, Tao; Hatzoglou, Maria.
Afiliação
  • Saikia M; Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA.
  • Jobava R; Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA.
  • Parisien M; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA.
  • Putnam A; Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, Ohio, USA.
  • Krokowski D; Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA.
  • Gao XH; Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA.
  • Guan BJ; Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA.
  • Yuan Y; Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA.
  • Jankowsky E; Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, Ohio, USA.
  • Feng Z; Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA.
  • Hu GF; Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts, USA.
  • Pusztai-Carey M; Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA.
  • Gorla M; Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, Andhra Pradesh, India.
  • Sepuri NB; Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, Andhra Pradesh, India.
  • Pan T; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA.
  • Hatzoglou M; Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA mxh8@case.edu.
Mol Cell Biol ; 34(13): 2450-63, 2014 Jul.
Article em En | MEDLINE | ID: mdl-24752898
ABSTRACT
Adaptation to changes in extracellular tonicity is essential for cell survival. However, severe or chronic hyperosmotic stress induces apoptosis, which involves cytochrome c (Cyt c) release from mitochondria and subsequent apoptosome formation. Here, we show that angiogenin-induced accumulation of tRNA halves (or tiRNAs) is accompanied by increased survival in hyperosmotically stressed mouse embryonic fibroblasts. Treatment of cells with angiogenin inhibits stress-induced formation of the apoptosome and increases the interaction of small RNAs with released Cyt c in a ribonucleoprotein (Cyt c-RNP) complex. Next-generation sequencing of RNA isolated from the Cyt c-RNP complex reveals that 20 tiRNAs are highly enriched in the Cyt c-RNP complex. Preferred components of this complex are 5' and 3' tiRNAs of specific isodecoders within a family of isoacceptors. We also demonstrate that Cyt c binds tiRNAs in vitro, and the pool of Cyt c-interacting RNAs binds tighter than individual tiRNAs. Finally, we show that angiogenin treatment of primary cortical neurons exposed to hyperosmotic stress also decreases apoptosis. Our findings reveal a connection between angiogenin-generated tiRNAs and cell survival in response to hyperosmotic stress and suggest a novel cellular complex involving Cyt c and tiRNAs that inhibits apoptosome formation and activity.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ribonuclease Pancreático / RNA de Transferência / Apoptose / Citocromos c / Apoptossomas / Clivagem do RNA Limite: Animals Idioma: En Revista: Mol Cell Biol Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ribonuclease Pancreático / RNA de Transferência / Apoptose / Citocromos c / Apoptossomas / Clivagem do RNA Limite: Animals Idioma: En Revista: Mol Cell Biol Ano de publicação: 2014 Tipo de documento: Article