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.
Genomics and Epigenetics Division, Garvan Institute of Medical Research Sydney, NSW, Australia ; Faculty of Medicine, St Vincent's Clinical School, University of New South Wales Sydney, NSW, Australia.
Jesper L V
JL
Maag
Department of Biomedicine and K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen Bergen, Norway.
Debabrata
D
Panja
Department of Biomedicine and K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen Bergen, Norway.
Ida
I
Sporild
Department of Biomedicine and K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen Bergen, Norway.
Sudarshan
S
Patil
Genomics and Epigenetics Division, Garvan Institute of Medical Research Sydney, NSW, Australia.
Dominik C
DC
Kaczorowski
Department of Biomedicine and K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen Bergen, Norway.
Clive R
CR
Bramham
Genomics and Epigenetics Division, Garvan Institute of Medical Research Sydney, NSW, Australia ; Faculty of Medicine, St Vincent's Clinical School, University of New South Wales Sydney, NSW, Australia.
Marcel E
ME
Dinger
Department of Biomedicine and K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen Bergen, Norway.
Karin
K
Wibrand
LTP (long term potentiation); long noncoding RNA (lncRNA); rat brain; repeat elements; retrotransposons; synaptic plasticity (LTP/LTD); time-series data