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A G-rich element forms a G-quadruplex and regulates BACE1 mRNA alternative splicing
Fisette JF, Montagna DR, Mihailescu MR, Wolfe MS.. Journal of neurochemistry, 2012-03-13
Topic: Brain proteins, microglia and lab models
β-Site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is the transmembrane aspartyl protease that catalyzes the first cleavage step in the proteolysis of the APP to the amyloid β-protein (Aβ), a process involved in the pathogenesis of Alzheimer disease. BACE1 pre-mRNA undergoes complex alternative splicing, the regulation of which is not well understood. We identified a G-rich sequence within exon 3 of BACE1 involved in controlling splice site selection.
Key findings
- BACE1 pre-mRNA undergoes complex alternative splicing, the regulation of which is not well understood.
- We identified a G-rich sequence within exon 3 of BACE1 involved in controlling splice site selection.
- Mutation of the G-rich sequence decreased use of the normal 5' splice site of exon 3, which leads to full-length and proteolytically active BACE1, and increased use of an alternative splice site, which leads to a shorter, essentially inactive isoform.
- Nuclease protection assays, nuclear magnetic resonance, and circular dichroism spectroscopy revealed that this sequence folds into a G-quadruplex structure.
Why it matters
This laboratory work identified a G-rich sequence in BACE1 that forms a G-quadruplex and helps control alternative splicing of the enzyme. It describes a basic mechanism of gene regulation, not a treatment or prevention for Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 42/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neurochemistry) |
| Journal's citation record | 3 / 4 | Journal of Neurochemistry: journal h-index 349 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2012 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 105 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.6 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 3 / 6 | Cited 3.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 17 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Michael S. Wolfe: h-index 36 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22303960) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 42 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1111/j.1471-4159.2012.07680.x
- PubMed: 22303960
- Original source →
- Free full text: Journal of Neurochemistry →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Fisette, J. F., Montagna, D. R., Mihailescu, M. R., & Wolfe, M. S. (2012). A G-rich element forms a G-quadruplex and regulates BACE1 mRNA alternative splicing. Journal of neurochemistry. https://doi.org/10.1111/j.1471-4159.2012.07680.x
Vancouver
Fisette JF, Montagna DR, Mihailescu MR, Wolfe MS. A G-rich element forms a G-quadruplex and regulates BACE1 mRNA alternative splicing. Journal of neurochemistry. 2012. doi:10.1111/j.1471-4159.2012.07680.x. PMID: 22303960.
BibTeX
@article{fisette2012-22303960,
author = {Fisette, J. F. and Montagna, D. R. and Mihailescu, M. R. and Wolfe, M. S.},
title = {{A G-rich element forms a G-quadruplex and regulates BACE1 mRNA alternative splicing}},
journal = {Journal of neurochemistry},
year = {2012},
doi = {10.1111/j.1471-4159.2012.07680.x},
pmid = {22303960},
url = {https://doi.org/10.1111/j.1471-4159.2012.07680.x}
}
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