Characterization of Small RNAs in Aplysia Reveals a Role for MiR-124 in Constraining Synaptic Plasticity Through CREB

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2009 Sep 26

PMID 19778509

Citations 224

Authors

Priyamvada Rajasethupathy

Ferdinando Fiumara

Robert Sheridan

Doron Betel

Sathyanarayanan V Puthanveettil

James J Russo

Chris Sander

Thomas Tuschl

Eric Kandel

Affiliations

Soon will be listed here.

Abstract

Memory storage and memory-related synaptic plasticity rely on precise spatiotemporal regulation of gene expression. To explore the role of small regulatory RNAs in learning-related synaptic plasticity, we carried out massive parallel sequencing to profile the small RNAs of Aplysia californica. We identified 170 distinct miRNAs, 13 of which were novel and specific to Aplysia. Nine miRNAs were brain enriched, and several of these were rapidly downregulated by transient exposure to serotonin, a modulatory neurotransmitter released during learning. Further characterization of the brain-enriched miRNAs revealed that miR-124, the most abundant and well-conserved brain-specific miRNA, was exclusively present presynaptically in a sensory-motor synapse where it constrains serotonin-induced synaptic facilitation through regulation of the transcriptional factor CREB. We therefore present direct evidence that a modulatory neurotransmitter important for learning can regulate the levels of small RNAs and present a role for miR-124 in long-term plasticity of synapses in the mature nervous system.

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References

Liu R, Fioravante D, Shah S, Byrne J . cAMP response element-binding protein 1 feedback loop is necessary for consolidation of long-term synaptic facilitation in Aplysia. J Neurosci. 2008; 28(8):1970-6. PMC: 6671429. DOI: 10.1523/JNEUROSCI.3848-07.2008. View

Lee R, Ambros V . An extensive class of small RNAs in Caenorhabditis elegans. Science. 2001; 294(5543):862-4. DOI: 10.1126/science.1065329. View

Puthanveettil S, Monje F, Miniaci M, Choi Y, Karl K, Khandros E . A new component in synaptic plasticity: upregulation of kinesin in the neurons of the gill-withdrawal reflex. Cell. 2008; 135(5):960-73. PMC: 2635114. DOI: 10.1016/j.cell.2008.11.003. View

Aravin A, Lagos-Quintana M, Yalcin A, Zavolan M, Marks D, Snyder B . The small RNA profile during Drosophila melanogaster development. Dev Cell. 2003; 5(2):337-50. DOI: 10.1016/s1534-5807(03)00228-4. View

Castellucci V, Pinsker H, Kupfermann I, Kandel E . Neuronal mechanisms of habituation and dishabituation of the gill-withdrawal reflex in Aplysia. Science. 1970; 167(3926):1745-8. DOI: 10.1126/science.167.3926.1745. View

Sutton M, Schuman E . Dendritic protein synthesis, synaptic plasticity, and memory. Cell. 2006; 127(1):49-58. DOI: 10.1016/j.cell.2006.09.014. View

Michlewski G, Guil S, Semple C, Caceres J . Posttranscriptional regulation of miRNAs harboring conserved terminal loops. Mol Cell. 2008; 32(3):383-93. PMC: 2631628. DOI: 10.1016/j.molcel.2008.10.013. View

Impey S, Obrietan K, Wong S, Poser S, Yano S, Wayman G . Cross talk between ERK and PKA is required for Ca2+ stimulation of CREB-dependent transcription and ERK nuclear translocation. Neuron. 1998; 21(4):869-83. DOI: 10.1016/s0896-6273(00)80602-9. View

Martin K, Zukin R . RNA trafficking and local protein synthesis in dendrites: an overview. J Neurosci. 2006; 26(27):7131-4. PMC: 6673931. DOI: 10.1523/JNEUROSCI.1801-06.2006. View

10.

Schratt G . Fine-tuning neural gene expression with microRNAs. Curr Opin Neurobiol. 2009; 19(2):213-9. DOI: 10.1016/j.conb.2009.05.015. View

11.

Lim L, Lau N, Garrett-Engele P, Grimson A, Schelter J, Castle J . Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005; 433(7027):769-73. DOI: 10.1038/nature03315. View

12.

Johnston R, Hobert O . A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature. 2003; 426(6968):845-9. DOI: 10.1038/nature02255. View

13.

Viswanathan S, Daley G, Gregory R . Selective blockade of microRNA processing by Lin28. Science. 2008; 320(5872):97-100. PMC: 3368499. DOI: 10.1126/science.1154040. View

14.

Hafner M, Landgraf P, Ludwig J, Rice A, Ojo T, Lin C . Identification of microRNAs and other small regulatory RNAs using cDNA library sequencing. Methods. 2007; 44(1):3-12. PMC: 2847350. DOI: 10.1016/j.ymeth.2007.09.009. View

15.

Ashraf S, McLoon A, Sclarsic S, Kunes S . Synaptic protein synthesis associated with memory is regulated by the RISC pathway in Drosophila. Cell. 2006; 124(1):191-205. DOI: 10.1016/j.cell.2005.12.017. View

16.

Reinhart B, Slack F, Basson M, Pasquinelli A, Bettinger J, Rougvie A . The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 2000; 403(6772):901-6. DOI: 10.1038/35002607. View

17.

Liu N, Okamura K, Tyler D, Phillips M, Chung W, Lai E . The evolution and functional diversification of animal microRNA genes. Cell Res. 2008; 18(10):985-96. PMC: 2712117. DOI: 10.1038/cr.2008.278. View

18.

Chi S, Zang J, Mele A, Darnell R . Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature. 2009; 460(7254):479-86. PMC: 2733940. DOI: 10.1038/nature08170. View

19.

Rybak A, Fuchs H, Smirnova L, Brandt C, Pohl E, Nitsch R . A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment. Nat Cell Biol. 2008; 10(8):987-93. DOI: 10.1038/ncb1759. View

20.

Castellucci V, Kandel E, Schwartz J, Wilson F, Nairn A, Greengard P . Intracellular injection of t he catalytic subunit of cyclic AMP-dependent protein kinase simulates facilitation of transmitter release underlying behavioral sensitization in Aplysia. Proc Natl Acad Sci U S A. 1980; 77(12):7492-6. PMC: 350531. DOI: 10.1073/pnas.77.12.7492. View