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Dynamic expression of long noncoding RNAs and repeat elements in synaptic plasticity


Long-term potentiation (LTP) of synaptic transmission is recognized as a cellular mechanism for learning and memory storage. Although de novo gene transcription is known to be required in the formation of stable LTP, the molecular mechanisms underlying synaptic plasticity remain elusive. Noncoding RNAs have emerged as major regulatory molecules that are abundantly and specifically expressed in the mammalian brain. By combining RNA-seq analysis with LTP induction in the dentate gyrus of live rats, we provide the first global transcriptomic analysis of synaptic plasticity in the adult brain. Expression profiles of mRNAs and long noncoding RNAs (lncRNAs) were obtained at 30 min, 2 and 5 h after high-frequency stimulation of the perforant pathway. The temporal analysis revealed dynamic expression profiles of lncRNAs with many positively, and highly, correlated to protein-coding genes with known roles in synaptic plasticity, suggesting their possible involvement in LTP. In light of observations suggesting a role for retrotransposons in brain function, we examined the expression of various classes of repeat elements. Our analysis identifies dynamic regulation of LINE1 and SINE retrotransposons, and extensive regulation of tRNA. These experiments reveal a hitherto unknown complexity of gene expression in long-term synaptic plasticity involving the dynamic regulation of lncRNAs and repeat elements. These findings provide a broader foundation for elucidating the transcriptional and epigenetic regulation of synaptic plasticity in both the healthy brain and in neurodegenerative and neuropsychiatric disorders.

Type Journal
ISBN 1662-4548 (Print) 1662-453X (Linking)
Authors Maag, J. L. ; Panja, D. ; Sporild, I. ; Patil, S. ; Kaczorowski, D. C. ; Bramham, C. R. ; Dinger, M. E. ; Wibrand, K.;
Responsible Garvan Author (missing name)
Publisher Name Front Neurosci
Published Date 2015-01-01
Published Volume 9
Published Pages 351
Status Published in-print
URL link to publisher's version
OpenAccess link to author's accepted manuscript version