A nuclear factor-binding domain in the 5'-untranslated region of the amyloid precursor protein promoter: implications for the regulation of gene expression

Topic: Brain proteins, microglia and lab models

Background The extracellular deposition of aggregated amyloid beta-protein is a neuropathological manifestation of Alzheimer disease and Down syndrome. The Amyloid beta-protein is derived from a group of larger differentially spliced proteins, the amyloid protein precursors (APP). Data suggests that the level of APP gene expression could contribute to the pathological processes leading to amyloid depositions. Findings The 5' untranslated region (UTR) of the APP gene, encompassing 147 base pairs between the transcriptional (+1) and the translational start site, was examined for its role in APP expression. Deletions close to the transcriptional start site reduced expression from the APP promoter in part by transcriptional mechanisms. However, deletions between position +50 and +104 had no effect on transcriptional activity while significantly reducing overall expression from the promoter. A nuclear factor-binding domain designated as DAPB was identified between position +72 and +115 of the 5'-APP-UTR. The binding-recognition sequence was localized between position +96 and +105. The same mutations that eliminated factor-binding also reduced expression from the APP promoter while having no effect on in vitro transcription or the RNA levels transcribed from transfected constructs. Conclusions A nuclear factor-binding domain designated as DAPB was identified in the 5'-UTR of the APP gene. Elimination of factor-binding correlated with an overall decline in expression from the APP promoter while in vitro transcription and the total amount of in vivo transcribed RNA remained unaffected. This suggests that the binding-factor may have a function in post-transcriptional regulation, including nuclear export of mRNA.

@article{vostrov2010-20205906,
  author  = {Vostrov, A. A. and Taheny, M. J. and Izkhakov, N. and Quitschke, W. W.},
  title   = {{A nuclear factor-binding domain in the 5'-untranslated region of the amyloid precursor protein promoter: implications for the regulation of gene expression}},
  journal = {BMC research notes},
  year    = {2010},
  doi     = {10.1186/1756-0500-3-4},
  pmid    = {20205906},
  url     = {https://doi.org/10.1186/1756-0500-3-4}
}

Key findings

• Data suggests that the level of APP gene expression could contribute to the pathological processes leading to amyloid depositions.
• However, deletions between position +50 and +104 had no effect on transcriptional activity while significantly reducing overall expression from the promoter.
• Elimination of factor-binding correlated with an overall decline in expression from the APP promoter while in vitro transcription and the total amount of in vivo transcribed RNA remained unaffected.
• This suggests that the binding-factor may have a function in post-transcriptional regulation, including nuclear export of mRNA.

Why it matters

This laboratory study identified a nuclear factor-binding domain in the 5' untranslated region of the amyloid precursor protein gene and found that eliminating factor binding reduced expression from the APP promoter. It is basic gene-regulation research and reports no treatment, cure or prevention for Alzheimer's disease.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1186/1756-0500-3-4
• PubMed: 20205906
• Original source →
• Free full text: BMC Research Notes →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

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