Friday, Mar.29, 2024
miRNA:

hsa-miR-659

Disease:

frontotemporal dementia

Relationship type:

Causal

Detection method for miRNA expression:

Northern blot, qRT-PCR etc

Expression pattern of miRNA:

normal

Validated targets of miRNA from the reference:

GRN

Validated targets of miRNA from TarBase:

unknown : More...

Predicted targets: MIRANDA, TARGETSCAN, PICTAR-VERT

 

Description:

Here we expand the role of GRN in FTLD-U and demonstrate that a common genetic variant (rs5848), located in the 3'untranslated region (UTR) of GRN in a binding-site for miR-659, is a major susceptibility factor for FTLD-U. In a series of pathologically confirmed FTLD-U patients without GRN mutations, we show that carriers homozygous for the T-allele of rs5848 have a 3.2-fold increased risk to develop FTLD-U compared to homozygous C-allele carriers (95% CI: 1.50-6.73). We further demonstrate that miR-659 can regulate GRN expression in vitro, with miR-659 binding more efficiently to the high risk T-allele of rs5848 resulting in augmented translational inhibition of GRN. A significant reduction in GRN protein was observed in homozygous T-allele carriers in vivo, through biochemical and immunohistochemical methods, mimicking the effect of heterozygous loss-of-function GRN mutations.

 

 

Reference:

Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia. | PMID:18723524
Rademakers R, Eriksen JL, Baker M, Robinson T, Ahmed Z, Lincoln SJ, Finch N, Rutherford NJ, Crook RJ, Josephs KA, Boeve BF
Hum Mol Genet. 2008 Aug 22. [Epub ahead of print]

 

 
 
 
  miRBase
  Tarbase
  miRGen
  miRGator
  CCBB
  MicroRNA.org
  miRRim
  miRNAMap 2.0
 
 
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