Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26572867
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Post-transcriptional regulation of SHANK3 expression by microRNAs related to
multiple neuropsychiatric disorders
#MMPMID26572867
Choi SY
; Pang K
; Kim JY
; Ryu JR
; Kang H
; Liu Z
; Kim WK
; Sun W
; Kim H
; Han K
Mol Brain
2015[Nov]; 8
(1
): 74
PMID26572867
show ga
BACKGROUND: Proper neuronal function requires tight control of gene dosage, and
failure of this process underlies the pathogenesis of multiple neuropsychiatric
disorders. The SHANK3 gene encoding core scaffolding proteins at glutamatergic
postsynapse is a typical dosage-sensitive gene, both deletions and duplications
of which are associated with Phelan-McDermid syndrome, autism spectrum disorders,
bipolar disorder, intellectual disability, or schizophrenia. However, the
regulatory mechanism of SHANK3 expression in neurons itself is poorly understood.
RESULTS: Here we show post-transcriptional regulation of SHANK3 expression by
three microRNAs (miRNAs), miR-7, miR-34a, and miR-504. Notably, the expression
profiles of these miRNAs were previously shown to be altered in some
neuropsychiatric disorders which are also associated with SHANK3 dosage changes.
These miRNAs regulated the expression of SHANK3 and other genes encoding
actin-related proteins that interact with Shank3, through direct binding sites in
the 3' untranslated region (UTR). Moreover, overexpression or inhibition of miR-7
and miR-504 affected the dendritic spines of the cultured hippocampal neurons in
a Shank3-dependent manner. We further characterized miR-504 as it showed the most
significant effect on both SHANK3 expression and dendritic spines among the three
miRNAs. Lentivirus-mediated overexpression of miR-504, which mimics its reported
expression change in postmortem brain tissues of bipolar disorder, decreased
endogenous Shank3 protein in cultured hippocampal neurons. We also revealed that
miR-504 is expressed in the cortical and hippocampal regions of human and mouse
brains. CONCLUSIONS: Our study provides new insight into the miRNA-mediated
regulation of SHANK3 expression, and its potential implication in multiple
neuropsychiatric disorders associated with altered SHANK3 and miRNA expression
profiles.
free
free
free
