LAUSR

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.Non-coding RNAs have been shown to be key components in translational regulation. Here the authors characterize long nucleolus specific lncRNA termed LoNA, identified to play a role in protein biosynthesis by inhibiting rRNA production and ribosome biosynthesis in nucleoli.