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  2. Genome-wide screening of NEAT1 regulators reveals cross-regulation between paraspeckles and mitochondria

Genome-wide screening of NEAT1 regulators reveals cross-regulation between paraspeckles and mitochondria

  • Nat Cell Biol. 2018 Oct;20(10):1145-1158. doi: 10.1038/s41556-018-0204-2.
Yang Wang 1 Shi-Bin Hu 1 2 Meng-Ran Wang 3 Run-Wen Yao 1 Di Wu 1 Li Yang 3 4 Ling-Ling Chen 5 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • 2 Department of Genetics, Stanford University, Stanford, CA, USA.
  • 3 Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • 4 School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • 5 State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. linglingchen@sibcb.ac.cn.
  • 6 School of Life Science and Technology, ShanghaiTech University, Shanghai, China. linglingchen@sibcb.ac.cn.
Abstract

The long noncoding RNA NEAT1 (nuclear enriched abundant transcript 1) nucleates the formation of paraspeckles, which constitute a type of nuclear body with multiple roles in gene expression. Here we identify NEAT1 regulators using an endogenous NEAT1 promoter-driven enhanced green fluorescent protein reporter in human cells coupled with genome-wide RNAi screens. The screens unexpectedly yield gene candidates involved in mitochondrial functions as essential regulators of NEAT1 expression and paraspeckle formation. Depletion of mitochondrial proteins and treatment of mitochondrial stressors both lead to aberrant NEAT1 expression via ATF2 as well as altered morphology and numbers of paraspeckles. These changes result in enhanced retention of mRNAs of nuclear-encoded mitochondrial proteins (mito-mRNAs) in paraspeckles. Correspondingly, NEAT1 depletion has profound effects on mitochondrial dynamics and function by altering the sequestration of mito-mRNAs in paraspeckles. Overall, our data provide a rich resource for understanding NEAT1 and paraspeckle regulation, and reveal a cross-regulation between paraspeckles and mitochondria.

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