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      PACT establishes a posttranscriptional brake on mitochondrial biogenesis by promoting the maturation of miR-181c

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      Author(s)
      Doğan, Aslı Ekin
      Hamid, Syed M.
      Yıldırım, Aslı Dilber
      Yıldırım, Zehra
      Sen, Ganes
      Riera, Celine E.
      Gottlieb, Roberta A.
      Erbay, Ebru
      Date
      2022-07
      Source Title
      Journal of Biological Chemistry
      Print ISSN
      00219258
      Publisher
      American Society for Biochemistry and Molecular Biology Inc.
      Volume
      298
      Issue
      7
      Pages
      1 - 15
      Language
      English
      Type
      Article
      Item Usage Stats
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      Abstract
      The double-stranded RNA-dependent protein kinase activating protein (PACT), an RNA-binding protein that is part of the RNA-induced silencing complex, plays a key role in miR-mediated translational repression. Previous studies showed that PACT regulates the expression of various miRs, selects the miR strand to be loaded onto RNA-induced silencing complex, and determines proper miR length. Apart from PACT's role in mediating the antiviral response in immune cells, what PACT does in other cell types is unknown. Strikingly, it has also been shown that cold exposure leads to marked downregulation of PACT protein in mouse brown adipose tissue (BAT), where mitochondrial biogenesis and metabolism play a central role. Here, we show that PACT establishes a posttranscriptional brake on mitochondrial biogenesis (mitobiogenesis) by promoting the maturation of miR-181c, a key suppressor of mitobiogenesis that has been shown to target mitochondrial complex IV subunit I (Mtco1) and sirtuin 1 (Sirt1). Consistently, we found that a partial reduction in PACT expression is sufficient to enhance mitobiogenesis in brown adipocytes in culture as well as during BAT activation in mice. In conclusion, we demonstrate an unexpected role for PACT in the regulation of mitochondrial biogenesis and energetics in cells and BAT. © 2022 The Authors
      Keywords
      Brown adipose tissue
      Micro-RNA
      Mitochondria
      Mitochondrial biogenesis
      RNAi
      Permalink
      http://hdl.handle.net/11693/111930
      Published Version (Please cite this version)
      https://dx.doi.org/10.1016/j.jbc.2022.102050
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