RGD Reference Report - Long Noncoding RNA FosDT Promotes Ischemic Brain Injury by Interacting with REST-Associated Chromatin-Modifying Proteins. - Rat Genome Database
Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Long Noncoding RNA FosDT Promotes Ischemic Brain Injury by Interacting with REST-Associated Chromatin-Modifying Proteins.

Authors: Mehta, SL  Kim, T  Vemuganti, R 
Citation: Mehta SL, etal., J Neurosci. 2015 Dec 16;35(50):16443-9. doi: 10.1523/JNEUROSCI.2943-15.2015.
RGD ID: 11068571
Pubmed: (View Article at PubMed) PMID:26674869
DOI: Full-text: DOI:10.1523/JNEUROSCI.2943-15.2015

Ischemia induces extensive temporal changes in cerebral transcriptome that influences the neurologic outcome after stroke. In addition to protein-coding RNAs, many classes of noncoding RNAs, including long noncoding RNAs (LncRNAs), also undergo changes in the poststroke brain. We currently evaluated the functional significance of an LncRNA called Fos downstream transcript (FosDT) that is cogenic with Fos gene. Following transient middle cerebral artery occlusion (MCAO) in adult rats, expression of FosDT and Fos was induced. FosDT knockdown significantly ameliorated the postischemic motor deficits and reduced the infarct volume. Focal ischemia also increased FosDT binding to chromatin-modifying proteins (CMPs) Sin3a and coREST (corepressors of the transcription factor REST). Furthermore, FosDT knockdown derepressed REST-downstream genes GRIA2, NFkappaB2, and GRIN1 in the postischemic brain. Thus, FosDT induction and its interactions with REST-associated CMPs, and the resulting regulation of REST-downstream genes might modulate ischemic brain damage. LncRNAs, such as FosDT, can be therapeutically targeted to minimize poststroke brain damage. SIGNIFICANCE STATEMENT: Mammalian brain is abundantly enriched with long noncoding RNAs (LncRNAs). Functional roles of LncRNAs in normal and pathological states are not yet understood. This study identified that LncRNA FosDT induced after transient focal ischemia modulates poststroke behavioral deficits and brain damage. These effects of FosDT in part are due to its interactions with chromatin-modifying proteins Sin3a and coREST (corepressors of the transcription factor REST) and subsequent derepression of REST-downstream genes GRIA2, NFkappaB2, and GRIN1. Therefore, LncRNA-mediated epigenetic remodeling could determine stroke outcome.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Grin1  (glutamate ionotropic receptor NMDA type subunit 1)

Genes (Mus musculus)
Grin1  (glutamate receptor, ionotropic, NMDA1 (zeta 1))

Genes (Homo sapiens)
GRIN1  (glutamate ionotropic receptor NMDA type subunit 1)


Additional Information