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Presenilin 1 mutation likely contributes to U1 small nuclear RNA dysregulation and Alzheimer's disease-like symptoms
Zhi Cheng, Yingchun Shang, Xinxin Xu, Zhiqiang Dong, Yongwang Zhang, Zhanqiang Du, Xinyi Lu, Tao Zhang. Neurobiology of aging, 2021-01-06
Topic: Genetics and APOE
Previous studies showed that U1 small nuclear RNA (snRNA) was selectively enriched in the brain of individuals with familial Alzheimer's disease (AD), resulting in widespread changes in RNA splicing. Our study further reported that presenilin-1 (PSEN1) induced an increase in U1 snRNA expression, accompanied by changed amyloid precursor protein expression, β-amyloid level, and cell death in SH-SY5Y cells. However, the effect of U1 snRNA overexpression on learning and memory is still unclear. In the present study, we found that neuronal U1 snRNA overexpression could generate U1 snRNA aggregates in the nuclear, accompanied by the widespread alteration of RNA splicing, resulting in the impairments of synaptic plasticity and spatial memory. In addition, more U1 snRNAs is bound to the intron binding sites accompanied by an increased intracellular U1 snRNA level. This suggests that U1 snRNA overexpression regulates RNA splicing and gene expression in neurons by manipulating the recruitment of the U1 snRNA to the nascent transcripts. Using in situ hybridization staining of human central nervous system-type neurons, we identified nuclear aggregates of U1 snRNA in neurons by upregulating the U1 snRNA level. Quantitative polymerase chain reaction analysis showed U1 snRNA accumulation in the insoluble fraction of neurons with PSEN1 mutation neurons rather than other types of U snRNAs. These results show an independent function of U1 snRNA in regulating RNA splicing, suggesting that aberrant RNA processing may mediate neurodegeneration induced by PSEN1 mutation.
Key findings
- Previous studies showed that U1 small nuclear RNA (snRNA) was selectively enriched in the brain of individuals with familial Alzheimer's disease (AD), resulting in widespread changes in RNA splicing.
- In the present study, we found that neuronal U1 snRNA overexpression could generate U1 snRNA aggregates in the nuclear, accompanied by the widespread alteration of RNA splicing, resulting in the impairments of synaptic plasticity and spatial memory.
- This suggests that U1 snRNA overexpression regulates RNA splicing and gene expression in neurons by manipulating the recruitment of the U1 snRNA to the nascent transcripts.
- These results show an independent function of U1 snRNA in regulating RNA splicing, suggesting that aberrant RNA processing may mediate neurodegeneration induced by PSEN1 mutation.
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Study details
- Evidence strengthLow
How this study scored 41/100
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. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 23 of the 56 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of aging) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 3 / 5 | 2021 — within 6 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33450722) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 23 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 23 of the 56 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
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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. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Cheng, Z., Shang, Y., Xu, X., Dong, Z., Zhang, Y., Du, Z., et al. (2021). Presenilin 1 mutation likely contributes to U1 small nuclear RNA dysregulation and Alzheimer's disease-like symptoms. Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2020.12.015
Vancouver
Cheng Z, Shang Y, Xu X, Dong Z, Zhang Y, Du Z, et al. Presenilin 1 mutation likely contributes to U1 small nuclear RNA dysregulation and Alzheimer's disease-like symptoms. Neurobiology of aging. 2021. doi:10.1016/j.neurobiolaging.2020.12.015. PMID: 33450722.
BibTeX
@article{cheng2021-33450722,
author = {Cheng, Zhi and Shang, Yingchun and Xu, Xinxin and Dong, Zhiqiang and Zhang, Yongwang and Du, Zhanqiang and Lu, Xinyi and Zhang, Tao},
title = {{Presenilin 1 mutation likely contributes to U1 small nuclear RNA dysregulation and Alzheimer's disease-like symptoms}},
journal = {Neurobiology of aging},
year = {2021},
doi = {10.1016/j.neurobiolaging.2020.12.015},
pmid = {33450722},
url = {https://doi.org/10.1016/j.neurobiolaging.2020.12.015}
}
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