RGD Reference Report - MicroRNA-101 regulates amyloid precursor protein expression in hippocampal neurons. - Rat Genome Database

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MicroRNA-101 regulates amyloid precursor protein expression in hippocampal neurons.

Authors: Vilardo, Elisa  Barbato, Christian  Ciotti, Mariateresa  Cogoni, Carlo  Ruberti, Francesca 
Citation: Vilardo E, etal., J Biol Chem. 2010 Jun 11;285(24):18344-51. doi: 10.1074/jbc.M110.112664. Epub 2010 Apr 15.
RGD ID: 14390059
Pubmed: PMID:20395292   (View Abstract at PubMed)
PMCID: PMC2881760   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M110.112664   (Journal Full-text)

The amyloid precursor protein (APP) and its proteolytic product amyloid beta (Abeta) are associated with both familial and sporadic forms of Alzheimer disease (AD). Aberrant expression and function of microRNAs has been observed in AD. Here, we show that in rat hippocampal neurons cultured in vitro, the down-regulation of Argonaute-2, a key component of the RNA-induced silencing complex, produced an increase in APP levels. Using site-directed mutagenesis, a microRNA responsive element (RE) for miR-101 was identified in the 3'-untranslated region (UTR) of APP. The inhibition of endogenous miR-101 increased APP levels, whereas lentiviral-mediated miR-101 overexpression significantly reduced APP and Abeta load in hippocampal neurons. In addition, miR-101 contributed to the regulation of APP in response to the proinflammatory cytokine interleukin-1beta (IL-lbeta). Thus, miR-101 is a negative regulator of APP expression and affects the accumulation of Abeta, suggesting a possible role for miR-101 in neuropathological conditions.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of amyloid precursor protein biosynthetic process involved_inIMP 14390059PMID:20395292ARUK-UCL 
response to interleukin-1 involved_inIDA 14390059PMID:20395292ARUK-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Ago2  (argonaute RISC catalytic component 2)
App  (amyloid beta precursor protein)


Additional Information