PMID- 22960213
OWN - NLM
STAT- MEDLINE
DCOM- 20130423
LR  - 20220311
IS  - 1943-2631 (Electronic)
IS  - 0016-6731 (Print)
IS  - 0016-6731 (Linking)
VI  - 192
IP  - 3
DP  - 2012 Nov
TI  - Activity-dependent human brain coding/noncoding gene regulatory networks.
PG  - 1133-48
LID - 10.1534/genetics.112.145128 [doi]
AB  - While most gene transcription yields RNA transcripts that code for proteins, a 
      sizable proportion of the genome generates RNA transcripts that do not code for 
      proteins, but may have important regulatory functions. The brain-derived 
      neurotrophic factor (BDNF) gene, a key regulator of neuronal activity, is 
      overlapped by a primate-specific, antisense long noncoding RNA (lncRNA) called 
      BDNFOS. We demonstrate reciprocal patterns of BDNF and BDNFOS transcription in 
      highly active regions of human neocortex removed as a treatment for intractable 
      seizures. A genome-wide analysis of activity-dependent coding and noncoding human 
      transcription using a custom lncRNA microarray identified 1288 differentially 
      expressed lncRNAs, of which 26 had expression profiles that matched 
      activity-dependent coding genes and an additional 8 were adjacent to or 
      overlapping with differentially expressed protein-coding genes. The functions of 
      most of these protein-coding partner genes, such as ARC, include long-term 
      potentiation, synaptic activity, and memory. The nuclear lncRNAs NEAT1, MALAT1, 
      and RPPH1, composing an RNAse P-dependent lncRNA-maturation pathway, were also 
      upregulated. As a means to replicate human neuronal activity, repeated 
      depolarization of SY5Y cells resulted in sustained CREB activation and produced 
      an inverse pattern of BDNF-BDNFOS co-expression that was not achieved with a 
      single depolarization. RNAi-mediated knockdown of BDNFOS in human SY5Y cells 
      increased BDNF expression, suggesting that BDNFOS directly downregulates BDNF. 
      Temporal expression patterns of other lncRNA-messenger RNA pairs validated the 
      effect of chronic neuronal activity on the transcriptome and implied various 
      lncRNA regulatory mechanisms. lncRNAs, some of which are unique to primates, thus 
      appear to have potentially important regulatory roles in activity-dependent human 
      brain plasticity.
FAU - Lipovich, Leonard
AU  - Lipovich L
AD  - Center for Molecular Medicine and Genetics, Wayne State University School of 
      Medicine, Detroit, Michigan 48202, USA
FAU - Dachet, Fabien
AU  - Dachet F
FAU - Cai, Juan
AU  - Cai J
FAU - Bagla, Shruti
AU  - Bagla S
FAU - Balan, Karina
AU  - Balan K
FAU - Jia, Hui
AU  - Jia H
FAU - Loeb, Jeffrey A
AU  - Loeb JA
LA  - eng
GR  - R01NS058802/NS/NINDS NIH HHS/United States
GR  - R01NS045207/NS/NINDS NIH HHS/United States
GR  - 1R03DA026021-01/DA/NIDA NIH HHS/United States
GR  - R03 DA026021/DA/NIDA NIH HHS/United States
GR  - R01 NS045207/NS/NINDS NIH HHS/United States
GR  - R01 NS058802/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120907
PL  - United States
TA  - Genetics
JT  - Genetics
JID - 0374636
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Untranslated)
SB  - IM
MH  - Brain/*metabolism
MH  - Brain-Derived Neurotrophic Factor/genetics
MH  - Cell Line
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation
MH  - *Gene Regulatory Networks
MH  - Humans
MH  - RNA, Long Noncoding/genetics
MH  - RNA, Messenger/genetics
MH  - *RNA, Untranslated
MH  - Transcription, Genetic
MH  - *Transcriptome
PMC - PMC3522156
EDAT- 2012/09/11 06:00
MHDA- 2013/04/24 06:00
PMCR- 2013/11/01
CRDT- 2012/09/11 06:00
PHST- 2012/09/11 06:00 [entrez]
PHST- 2012/09/11 06:00 [pubmed]
PHST- 2013/04/24 06:00 [medline]
PHST- 2013/11/01 00:00 [pmc-release]
AID - genetics.112.145128 [pii]
AID - 145128 [pii]
AID - 10.1534/genetics.112.145128 [doi]
PST - ppublish
SO  - Genetics. 2012 Nov;192(3):1133-48. doi: 10.1534/genetics.112.145128. Epub 2012 
      Sep 7.