Activity dependent LoNA regulates translation by coordinating rRNA transcription and methylation

Dingfeng Li, Juan Zhang, Ming Wang, Xiaohui Li, Huarui Gong, Huiping Tang, Lin Chen, Lili Wan and Qiang Liu ()
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Dingfeng Li: University of Science and Technology of China
Juan Zhang: University of Science and Technology of China
Ming Wang: University of Science and Technology of China
Xiaohui Li: University of Science and Technology of China
Huarui Gong: University of Science and Technology of China
Huiping Tang: University of Science and Technology of China
Lin Chen: University of Science and Technology of China
Lili Wan: University of Pennsylvania
Qiang Liu: University of Science and Technology of China

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04072-4

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