2. Academic Validation
  3. Activity dependent LoNA regulates translation by coordinating rRNA transcription and methylation

Activity dependent LoNA regulates translation by coordinating rRNA transcription and methylation

  • Nat Commun. 2018 Apr 30;9(1):1726. doi: 10.1038/s41467-018-04072-4.
Dingfeng Li 1 2 3,  Juan Zhang 1 2 3,  Ming Wang 1 2,  Xiaohui Li 1 2 3,  Huarui Gong 1 2,  Huiping Tang 1 2,  Lin Chen 1 2,  Lili Wan 4,  Qiang Liu 5 6 7 8
Affiliations

Affiliations

  • 1 Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, 230026, China.
  • 2 CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, 230026, China.
  • 3 Neurodegenerative Disease Research Center, University of Science and Technology of China, Hefei, 230026, China.
  • 4 Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • 5 Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, 230026, China. liuq2012@ustc.edu.cn.
  • 6 CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, 230026, China. liuq2012@ustc.edu.cn.
  • 7 Neurodegenerative Disease Research Center, University of Science and Technology of China, Hefei, 230026, China. liuq2012@ustc.edu.cn.
  • 8 National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei, 230029, China. liuq2012@ustc.edu.cn.
PMID: 29712923 DOI: 10.1038/s41467-018-04072-4
Abstract

The ribosome is indispensable for precisely controlling the capacity of protein synthesis. However, how translational machinery is coordinated to meet the translational demands remains elusive. Here, we identify a nucleolar-specific lncRNA (LoNA), its 5' portion binds and sequesters nucleolin to suppress rRNA transcription, and its snoRNA like 3' end recruits and diminishes fibrillarin activity to reduce rRNA methylation. Activity-dependent decrease of LoNA leads to elevated rRNA and ribosome levels, an increased proportion of polysomes, mRNA polysome loading, and protein translation. In addition, transport of ribosomes to synapses is particularly promoted, resulting in increased levels of AMPA/NMDA Receptor, enhanced synaptic plasticity, long-term potentiation and consolidated memory. Strikingly, hippocampal LoNA deficiency not only enhances long-term memory in WT mice, but also restores impaired memory function in APP/PS1 transgenic mice. Together, these findings reveal the multifaceted role of LoNA in modulating ribosome biogenesis to meet the translational demands of long-term memory.

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