Activity Dependent LoNA Regulates Translation by Coordinating RRNA Transcription and Methylation

Overview

Journal Nat Commun

Specialty Biology

Date 2018 May 2

PMID 29712923

Citations 56

Authors

Dingfeng Li

Juan Zhang

Ming Wang

Xiaohui Li

Huarui Gong

Huiping Tang

Lin Chen

Lili Wan

Qiang Liu

Affiliations

Soon will be listed here.

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.

Citing Articles

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References

Joseph G, Amalric F, Bouvet P . Nucleolin is a sequence-specific RNA-binding protein: characterization of targets on pre-ribosomal RNA. J Mol Biol. 1996; 260(1):34-53. DOI: 10.1006/jmbi.1996.0380. View

Jantzen H, Admon A, Bell S, Tjian R . Nucleolar transcription factor hUBF contains a DNA-binding motif with homology to HMG proteins. Nature. 1990; 344(6269):830-6. DOI: 10.1038/344830a0. View

McGaugh J . Memory--a century of consolidation. Science. 2000; 287(5451):248-51. DOI: 10.1126/science.287.5451.248. View

Pietrzak M, Rempala G, Nelson P, Zheng J, Hetman M . Epigenetic silencing of nucleolar rRNA genes in Alzheimer's disease. PLoS One. 2011; 6(7):e22585. PMC: 3142181. DOI: 10.1371/journal.pone.0022585. View

Wu L, Wells D, Tay J, Mendis D, Abbott M, Barnitt A . CPEB-mediated cytoplasmic polyadenylation and the regulation of experience-dependent translation of alpha-CaMKII mRNA at synapses. Neuron. 1998; 21(5):1129-39. DOI: 10.1016/s0896-6273(00)80630-3. View

Erard M, Belenguer P, Caizergues-Ferrer M, Pantaloni A, Amalric F . A major nucleolar protein, nucleolin, induces chromatin decondensation by binding to histone H1. Eur J Biochem. 1988; 175(3):525-30. DOI: 10.1111/j.1432-1033.1988.tb14224.x. View

Si K, Giustetto M, Etkin A, Hsu R, Janisiewicz A, Miniaci M . A neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in aplysia. Cell. 2003; 115(7):893-904. DOI: 10.1016/s0092-8674(03)01021-3. View

Allen K, Gourov A, Harte C, Gao P, Lee C, Sylvain D . Nucleolar integrity is required for the maintenance of long-term synaptic plasticity. PLoS One. 2014; 9(8):e104364. PMC: 4121280. DOI: 10.1371/journal.pone.0104364. View

Lin J, Lai S, Jia R, Xu A, Zhang L, Lu J . Structural basis for site-specific ribose methylation by box C/D RNA protein complexes. Nature. 2011; 469(7331):559-63. DOI: 10.1038/nature09688. View

10.

Payao S, Smith M, Toniolo J . Investigation of the nucleolar organizer regions in Alzheimer's disease. Gerontology. 1994; 40(1):13-7. DOI: 10.1159/000213569. View

11.

Kiss T . Small nucleolar RNAs: an abundant group of noncoding RNAs with diverse cellular functions. Cell. 2002; 109(2):145-8. DOI: 10.1016/s0092-8674(02)00718-3. View

12.

Gilbert W . Functional specialization of ribosomes?. Trends Biochem Sci. 2011; 36(3):127-32. PMC: 3056915. DOI: 10.1016/j.tibs.2010.12.002. View

13.

Lacar B, Linker S, Jaeger B, Krishnaswami S, Barron J, Kelder M . Nuclear RNA-seq of single neurons reveals molecular signatures of activation. Nat Commun. 2016; 7:11022. PMC: 4838832. DOI: 10.1038/ncomms11022. View

14.

Incarnato D, Anselmi F, Morandi E, Neri F, Maldotti M, Rapelli S . High-throughput single-base resolution mapping of RNA 2΄-O-methylated residues. Nucleic Acids Res. 2017; 45(3):1433-1441. PMC: 5388417. DOI: 10.1093/nar/gkw810. View

15.

Iacono D, OBrien R, Resnick S, Zonderman A, Pletnikova O, Rudow G . Neuronal hypertrophy in asymptomatic Alzheimer disease. J Neuropathol Exp Neurol. 2008; 67(6):578-89. PMC: 2518071. DOI: 10.1097/NEN.0b013e3181772794. View

16.

Scheetz A, Nairn A, Constantine-Paton M . NMDA receptor-mediated control of protein synthesis at developing synapses. Nat Neurosci. 2000; 3(3):211-6. DOI: 10.1038/72915. View

17.

Grummt I, Pikaard C . Epigenetic silencing of RNA polymerase I transcription. Nat Rev Mol Cell Biol. 2003; 4(8):641-9. DOI: 10.1038/nrm1171. View

18.

Martin K, Ephrussi A . mRNA localization: gene expression in the spatial dimension. Cell. 2009; 136(4):719-30. PMC: 2819924. DOI: 10.1016/j.cell.2009.01.044. View

19.

Kacharmina J, Job C, Crino P, Eberwine J . Stimulation of glutamate receptor protein synthesis and membrane insertion within isolated neuronal dendrites. Proc Natl Acad Sci U S A. 2000; 97(21):11545-50. PMC: 17237. DOI: 10.1073/pnas.97.21.11545. View

20.

Durut N, Saez-Vasquez J . Nucleolin: dual roles in rDNA chromatin transcription. Gene. 2014; 556(1):7-12. DOI: 10.1016/j.gene.2014.09.023. View