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AGO CLIP Reveals an Activated Network for Acute Regulation of Brain Glutamate Homeostasis in Ischemic Stroke.
Kobayashi, Mariko; Benakis, Corinne; Anderson, Corey; Moore, Michael J; Poon, Carrie; Uekawa, Ken; Dyke, Jonathan P; Fak, John J; Mele, Aldo; Park, Christopher Y; Zhou, Ping; Anrather, Josef; Iadecola, Costantino; Darnell, Robert B.
Afiliación
  • Kobayashi M; Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: mkobayashi@rockefeller.edu.
  • Benakis C; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61(st) Street, New York, NY 10065, USA.
  • Anderson C; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61(st) Street, New York, NY 10065, USA.
  • Moore MJ; Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
  • Poon C; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61(st) Street, New York, NY 10065, USA.
  • Uekawa K; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61(st) Street, New York, NY 10065, USA.
  • Dyke JP; Department of Radiology, Citigroup Biomedical Imaging Center, Weill Cornell Medicine, 516 East 72(nd) Street, New York, NY 10021, USA.
  • Fak JJ; Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
  • Mele A; Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
  • Park CY; Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
  • Zhou P; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61(st) Street, New York, NY 10065, USA.
  • Anrather J; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61(st) Street, New York, NY 10065, USA.
  • Iadecola C; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61(st) Street, New York, NY 10065, USA.
  • Darnell RB; Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: darnelr@rockefeller.edu.
Cell Rep ; 28(4): 979-991.e6, 2019 07 23.
Article en En | MEDLINE | ID: mdl-31340158
Post-transcriptional regulation by microRNAs (miRNAs) is essential for complex molecular responses to physiological insult and disease. Although many disease-associated miRNAs are known, their global targets and culminating network effects on pathophysiology remain poorly understood. We applied Argonaute (AGO) crosslinking immunoprecipitation (CLIP) to systematically elucidate altered miRNA-target interactions in brain following ischemia and reperfusion (I/R) injury. Among 1,190 interactions identified, the most prominent was the cumulative loss of target regulation by miR-29 family members. Integration of translational and time-course RNA profiles revealed a dynamic mode of miR-29 target de-regulation, led by acute translational activation and a later increase in RNA levels, allowing rapid proteomic changes to take effect. These functional regulatory events rely on canonical and non-canonical miR-29 binding and engage glutamate reuptake signals, such as glial glutamate transporter (GLT-1), to control local glutamate levels. These results uncover a miRNA target network that acts acutely to maintain brain homeostasis after ischemic stroke.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Isquemia Encefálica / Ácido Glutámico / Accidente Cerebrovascular / Reactivos de Enlaces Cruzados / Proteínas Argonautas / Homeostasis Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Isquemia Encefálica / Ácido Glutámico / Accidente Cerebrovascular / Reactivos de Enlaces Cruzados / Proteínas Argonautas / Homeostasis Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos